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Biomedical subjects

A A Hart

Publications and source records attributed to A A Hart.

At least 91 records · Page 5Linked to original sources
PubMed1995

DNA index and %S-phase cells determined in acute lymphoblastic leukemia of children: a report from studies ALL V, ALL VI, and ALL VII (1979-1991) of the Dutch Childhood Leukemia Study Group and The Netherlands Workgroup on Cancer Genetics and Cytogenetics.

DNA per cell content was routinely recorded by single-parameter flow cytometry in leukemic blasts from 473 children with acute lymphoblastic leukemia (ALL), enrolled in national studies ALL V, VI, and VII (1979-1991) of the Dutch Childhood Leukemia Study Group. The parameters bonemarrow %S-value and DNA Index were compared with clinical features, with chromosome number based on cytogenetic analyses and with treatment results in study ALL VI. %S-values, ranging between 1 and 36%, were unrelated to initial white blood cell count, immunophenotype, and DNA index but were lowest in blasts with L1 morphology. In study ALL VI (non-high risk), the survival of patients with < or = 6% S-phase cells was superior to that of patients with %S-values of > 6 (P = 0.030). Hyperdiploidy, defined by a DNA index > or = 1.16, was compared to the cytogenetic hyperdiploid classification of n > 50. Initially there were 25 discrepancies in 189 samples jointly analysed by flow cytometry and cytogenetics. After review only five discrepancies remained unresolved. Hyperdiploidy, independent of the method used, was found to be unrelated to blast morphology and %S-phase cells but closely associated with c-ALL and was absent in T-ALL. In study ALL VI, event-free survival at 8 years of hyperdiploid patients was 90.6% but was not significantly different from non-hyperdiploid patients (EFS = 82.1%; P = 0.08). Routine DNA flow cytometry appeared a valuable adjunct to cytogenetic analyses and allowed the identification of a large subset of non-high-risk ALL patients in study ALL VI with a DNA index > or = 1.16 or %S-value of < or = 6.0 with highest survival probability.

Bone Marrow↗
PubMed1995

Separation of multiple genes controlling the T-cell proliferative response to IL-2 and anti-CD3 using recombinant congenic strains.

T lymphocytes of the strain BALB/cHeA exhibit a low proliferative response to IL-2 and a high response to the anti-CD3 monoclonal antibodies, while the strain STS/A lymphocyte response to these stimuli is the opposite. We analyzed the genetic basis of this strain difference, using a novel genetic tool: the recombinant congenic strains (RCS). Twenty BALB/c-c-STS/Dem (CcS/Dem) RCS were used, each containing a different random set of approximately 12.5% of the genes from STS and the remainder from BALB/c. Consequently, the genes participating in the multigenic control of a phenotypic difference between BALB/c and STS become separated into different CcS strains where they can be studied individually. The strain distribution patterns of the proliferative responses to IL-2 and anti-CD3 in the CcS strains are different, showing that different genes are involved. The large differences between individual CcS strains in response to IL-2 or anti-CD3 indicate that both reactions are controlled by a limited number of genes with a relatively large effect. The high proliferative response to IL-2 is a dominant characteristic. It is not caused by a larger major cell subset size, nor by a higher level of IL-2R expression. The response to anti-CD3 is known to be controlled by polymorphism in Fc gamma receptor 2 (Fcgr2) and the CcS strains carrying the low responder Fcgr2 allele indeed responded weakly. However, as these strains do respond to immobilized anti-CD3, while the STS strain does not, and as some CcS strains with the BALB/c allele of Fcgr2 are also low responders, additional gene(s) of the STS strain strongly depress the anti-CD3 response. In a backcross between the high responder and the low responder strains CcS-9 and CcS-11, one of these unknown genes was mapped to the chromosome 10 near D10Mit14. The CcS mouse strains which carry the STS alleles of genes controlling the proliferative response to IL-2 and anti-CD3 allow the future mapping, cloning, and functional analysis of these genes and the study of their biological effects in vivo.

Animals↗
PubMed1995

Provider-associated factors in obstetric interventions.

OBJECTIVE: To assess which factors influence provider-associated differences in obstetric interventions. STUDY DESIGN: A survey of obstetricians and co-workers in a sample consisting of 38 Dutch hospitals was taken, using a questionnaire that contained questions about personal and hospital-policy data, and 19 clinical problems with a choice between intervention and non-intervention. From the clinical problems an Intervention Score was assembled. The influence of the personal and hospital-policy items on this Intervention Score was studied by analysis of variance. RESULTS: Overall the Intervention Score was low, with considerable interindividual variation. Four personal/hospital items influenced the Intervention Score: the teacher could affect the score in either direction; the increasing age of the obstetrician and routine electronic fetal monitoring had an increasing effect; employment of midwives had a decreasing effect. Other factors, including litigation, had no effect. CONCLUSION: Supplier-induced differences do exist in obstetric interventions and are influenced by personal and hospital-policy factors.

Adult↗
PubMed1995

The prognostic significance of the axillary apex biopsy in clinically operable breast cancer.

To evaluate the prognostic significance of the axillary apex biopsy and its impact on clinical practice, a retrospective analysis was performed in 875 patients with clinically operable breast cancer who underwent this procedure from 1977 to 1985 (165 TNM stage I; 512 TNM stage II; 198 TNM stage IIIA). Apex biopsy is performed as a staging procedure. Apex biopsy positive patients are treated by radiotherapy alone, while apex biopsy negative patients are treated with breast conserving therapy or mastectomy, both including complete axillary dissection. The apex biopsy was tumour positive in 4% of TNM stage I patients; 17% of stage II patients and 40% of stage IIIA patients. Among patients with clinically node-negative disease, the apex biopsy was positive in 12%; in patients with palpable suspected lymph nodes this figure was 45%. Actuarial 8 y survival rates for patients with stage I, II and III disease and a negative apex biopsy were 83, 70 and 50%, respectively. The corresponding figures for patients with a positive apex biopsy were 60, 28 and 14%. In a multivariate analysis, a positive apex biopsy, clinical N classification and T classification were independent prognostic factors for survival (P < 0.0001). We conclude that a positive apex biopsy is rare in clinical stage I breast cancer, and that in patients with TNM stage II and III disease the procedure is an important tool to assess prognosis pre-operatively.

Axilla↗
PubMed1995

Carcinoma of the pyriform sinus: a retrospective analysis of treatment results over a 20-year period.

One hundred and one patients with pyriform sinus carcinoma treated at the Netherlands Cancer Institute were studied retrospectively. The patients were staged according to the UICC criteria of 1987: there were no stage I, 23 stage II, 30 stage III, and 48 stage IV patients. The treatment consisted of radiotherapy (n = 45), a planned combination of surgery and post-operative radiotherapy (n = 47) or surgery alone (n = 9). The crude 5-year survival was 27%, whereas the 5-year disease-free survival was 37%. The locoregional disease-free survival was 52%. Stage according to the UICC 1987 criteria is an important prognostic variable (P = 0.0026). Furthermore, significantly less locoregional recurrences and a better disease-free survival were seen in the combined surgery and radiotherapy group than in the exclusively irradiated group (P < 0.0001).

Adult↗
PubMed1995

Pulmonary resection for metastases of colorectal origin.

STUDY OBJECTIVE: To develop selection criteria for pulmonary metastasectomy in patients with metastases of colorectal cancer confined to the lungs. DESIGN: A retrospective study. SETTING: Medical records of all patients operated on for this condition in the Netherlands in the period 1982 to 1992 (n = 38). INTERVENTION: Evaluation by means of Cox's proportional hazards regression analysis of factors, which might relate to postthoracotomy disease-free survival and/or postthoracotomy survival. MEASUREMENTS AND RESULTS: The 5-year disease-free survival was 31%, and the overall 5-year survival was 43% (Kaplan-Meyer). Multivariately, a number of three or fewer metastases (p = 0.012) and a short delay between detection of pulmonary metastases and resection (p = 0.05) related to a longer postthoracotomy disease-free interval. A longer interval between resection of the primary tumor and detection of lung metastases related to a longer postthoracotomy survival (p = 0.021). CONCLUSIONS: Patients with three or less pulmonary metastases of colorectal origin may benefit from resection; once metastases have been detected, resection should not be postponed.

Adult↗
PubMed1994

Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer.

BACKGROUND: The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer. METHODS: Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked immunosorbent assay technique for reactivity with HPV-16 E4 (E401p) and E7 (E701p) synthetic peptides. The presence and serum level of these antibodies were correlated with tumor stage, histologic features, and prognostic parameters. RESULTS: The median follow-up was 65 months (range, 6-97 months). Antibodies to E401p peptide were found in 5 of the 198 (3%) control subjects, 4 of the 43 (9%) patients with low tumor stage (International Federation of Gynecology and Obstetrics [FIGO] Ia, Ib, IIa), and 7 of the 35 (20%) patients with advanced tumor stage (FIGO IIb, III, IVa). Antibodies to E701p were found in 25 (13%), 11 (26%), and 11 (31%) women, respectively. The differences between patients and control subjects were significant (P < 0.002). Seropositivity against these peptides showed no correlation with tumor stage. Antibody levels to both peptides were significantly higher in patients compared with control subjects (P < 0.05). Furthermore, antibody levels to E401p were higher in patients with advanced tumor stage versus patients with low tumor stage (P = 0.0097). Such a relation was not found for anti-E701p antibodies. In the univariate analysis, a high level of anti-E701p antibodies was associated with a shorter disease free interval (P = 0.012) and poor survival (P = 0.049). However, this variable possessed no prognostic value after adjusting for FIGO stage and tumor size. CONCLUSIONS: The authors' findings indicate that the prognostic significance of serum antibodies to the HPV-16 E4 and E7 peptides used in this study of patients with cervical cancer is limited.

Adult↗
PubMed1994

Resectable retroperitoneal soft tissue sarcomas. The effect of extent of resection and postoperative radiation therapy on local tumor control.

BACKGROUND: Soft tissue malignancies of the retroperitoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities. METHODS: From 1973 to 1990, 34 patients were initially treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands Cancer Institute. In a retrospective study, the prognostic effect of extent of primary surgery and postoperative radiation therapy was examined. RESULTS: Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most commonly found. Grade of malignancy was defined as medium to high (II/III) in 44% and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was achieved in 29 patients. After complete resection, the 5-year survival rate and the local recurrence rate were 35% and 63%, respectively. Extended surgery (performed in eight patients) showed a local recurrence rate of 50%. Thirteen patients received high-dose postoperative radiation therapy, which was found to have a significant favorable effect on the recurrence-free interval (P < 0.01). CONCLUSIONS: We conclude that complete (extended) resection followed by high-dose postoperative radiation therapy improves the prognostic outcome of patients with retroperitoneal soft tissue sarcomas.

Adult↗
PubMed1994

Hereditary motor and sensory neuropathy type I: clinical and neurographical features of the 17p duplication subtype.

Forty-four affected individuals, aged 8-68 years (mean 34 years), from six families with hereditary motor and sensory neuropathy type I (HMSN I, Charcot-Marie-Tooth disease type 1) were investigated to determine the clinical and electroneurographical characteristics of the HMSN I subtype that is defined by the presence of a DNA duplication on chromosome 17p. Motor nerve conduction velocity (MNCV) and, to a lesser extent, compound muscle action potential amplitude, were inversely related to clinical severity. Neither clinical severity nor MNCV were significantly related to age. These results suggest that the primary pathological process is not, or only slightly active after childhood.

Action Potentials↗
PubMed1994

Prognostic significance of serum fragments of cytokeratin 19 measured by Cyfra 21-1 in cervical cancer.

Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed.

Adult↗
PubMed1994

Quantification of patient to patient variation of skin erythema developing as a response to radiotherapy.

A method is described to determine accurately skin redness during a course of radiotherapy using reflectance spectroscopy utilizing information from across the visible spectrum according to the L*a*b* color coordinate system. The method was used to quantify the development of skin erythema during and after electron beam irradiation of the chest wall following mastectomy. A number of factors were identified which could influence the wide variation in response seen between patients. These were: intra- and inter-observer variation; intra- and inter-patient variation and variation in the actual dose delivered. Statistical analysis, including an analysis of variance of inter- and intra-patient variation, revealed that the major factor that accounts for the observed difference between patients is a true inter-patient variation, with a coefficient of variation, corrected for intra-patient variation, of 43%. Within the narrow dose range administered in this study, there was no demonstrable dose-effect relationship, raising questions about the role of cell death in the basal layer of the epidermis in the pathogenesis of radiation induced erythema.

Adult↗
PubMed1994

Limb-sparing therapy of extremity soft tissue sarcomas: treatment outcome and long-term functional results.

The purpose of this study is to assess the long-term success rate and functional results of limb-sparing therapy in a group of 156 patients with soft tissue sarcomas of the extremities in the Netherlands Cancer Institute, treated according to a standard protocol of surgery and radiotherapy, if indicated. The patients (79 females and 77 males) were treated between 1977 and 1983 by an intended wide local excision with a margin of at least 2 cm. Postoperative radiotherapy was applied in 117 patients; 26 patients had surgery only, including 13 patients who had to be treated by amputation. The total dose was 60 Gy, with 40 Gy to a large volume and a boost of 20 Gy to the tumour bed at 2 Gy per fraction, five fractions per week. Most sarcomas were located in the proximal part of the lower extremity (51%). The group comprised 50 liposarcomas, 47 malignant fibrous hystiocystoma (MFH) and 59 other histologies; 69 (44%) had high-grade tumours. Three treatment groups with limb-sparing treatment were defined: group I (n = 26) patients who had a complete excision receiving no further treatment, group II (n = 64) with narrow surgical margins and radiotherapy and group III (n = 53) with incomplete resection and radiotherapy. The 10-year actuarial overall survival and local control rate for all patients was 63 and 81%, respectively. Multivariate analysis showed that histological grade (P < 0.0001), age (P = 0.0005) and location deep to the fascia (P = 0.0008) were independent prognostic factors for survival, while local control was predicted by grade (P = 0.0014) and treatment group (p = 0.028). Patients with surgery only (group I) had 81% 5-year local control as compared to 92% with radiotherapy after narrow surgery (group II) and 74% with incomplete surgery and radiotherapy (group III). Limb preservation when attempted was achieved in 90% of the patients. After limb-sparing treatment, 7% had severe impairment of mobility, 3% had lymph oedema and 16% marked fibrosis. Fractures in the irradiated bone occurred in 6% of the patients. The combination of limited surgery followed by radiotherapy resulted in a high local control rate with good functional results. Ultimately limb sparing treatment was successful in 83% of all patients with extremity sarcomas.

Adolescent↗
PubMed1994

Management of bowel obstruction in patients with advanced ovarian cancer.

In a retrospective study, 58 patients with bowel obstruction due to advanced ovarian cancer were analysed. In a forward stepwise proportional hazard regression analysis, we looked for factors influencing bowel obstruction-free survival. Patients who presented with bowel obstruction as the first sign of ovarian cancer and those with a longer interval between last cancer treatment and bowel obstruction did better. Patients with ascites did worse. No other independent factors were found. Based on these data, we classified patients into a favourable prognosis group (no previous treatment or interval since last treatment exceeding 6 months; no ascites) and a poor prognosis group (interval since last treatment shorter than 6 months; ascites). Patients from the favourable prognosis group had a median bowel obstruction-free survival of 8 months, compared to 1 month for the poor prognosis group (P < 0.001). Surgery had a marginally significant positive effect on bowel obstruction-free survival when compared to medical treatment in the favourable prognosis group (P = 0.052). Surgery had no effect at all in the poor prognosis patients.

Adult↗
PubMed1994

Kras-2 alleles, mutations, and lung tumor susceptibility in the mouse--an evaluation.

Lung Tumor Susceptibility (LTS) in the mouse has been shown to be influenced by loci within the Major Histocompatibility Complex (MHC) and the Kras-2 regions. In crosses between susceptible and resistant strains, one allele of Kras-2 has been linked with a high LTS, whereas the other allele has been linked with a low LTS. Furthermore, these Kras-2 alleles affect differently the occurrence of Kras-2 mutations in lung tumors. In this study we evaluated the relationship between LTS, Kras-2 alleles and Kras-2 mutations, using Recombinant Congenic Strains with identical MHC haplotypes. The Kras-2 region indeed influences the frequency of Kras-2 mutations in N-ethyl-N-nitrosourea-induced lung tumors. These mutations are associated with larger tumors. However, Kras-2 affects LTS only marginally. Several strains with identical Kras-2 alleles and mutation frequency differ widely in LTS, while some strains with different alleles and mutation frequency do not. We conclude that a considerable part of the genetic variability in LTS is caused by LTS-loci other than Kras-2 and MHC.

Alleles↗
PubMed1994

Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion.

To date, little is known about prognostic factors for limb recurrence-free interval and survival in patients with recurrent melanoma of the limbs treated with regional isolated perfusion. Therefore, 216 such patients treated with normothermic perfusion using melphalan during the period 1978 to 1990 were analyzed for patient and tumor related variables using a Cox proportional hazard model. The five year limb recurrence-free interval was 52 percent. For stage II (n = 67), IIIA (n = 71) and IIIAB and IIIB (n = 78) disease separately, these percentages were 53, 56 and 47 percent. In stage II disease, patients with a local recurrence adjacent to scar or skin graft had a significantly better five year limb recurrence-free interval than patients with satellites (75 versus 33 percent; p = 0.0009). Prognostic factors for limb recurrence-free interval were--in order of importance--tumor tissue left in situ, number of previous limb recurrences and total tumor surface area. The overall five year survival rate was 42 percent. For stages II, IIIA and IIIAB and IIIB disease, these percentages were 57, 45 and 25 percent, respectively. There was no survival benefit for patients with a local recurrence. Prognostic factors for survival were, in order of importance, stage of disease, gender, age, Breslow thickness, Clark level of infiltration of the primary melanoma and the number of lesions forming the indication for perfusion. The results of this study will eventually further delineate indications for perfusion.

Adult↗
PubMed1994

Prognostic factors for tumor response and limb recurrence-free interval in patients with advanced melanoma of the limbs treated with regional isolated perfusion with melphalan.

BACKGROUND: At this time little is known about prognostic factors for tumor response and subsequent limb recurrence-free interval in patients suffering from advanced melanoma of the limbs who were treated with regional isolated perfusion. METHODS: A retrospective analysis was done, with a logistic regression model and a Cox proportional hazard analysis, looking at possible patient-, tumor-, and treatment-related prognostic factors in all 120 patients with advanced melanoma of the limbs who were treated with regional isolated perfusion with melphalan in the period 1978 to 1990 at our institutions. RESULTS: Complete remission was achieved in 65 patients (54%) with a median duration of 9+ months (range, 1 to 97+ months), and partial remission was seen in 30 patients (25%). Prognostic factors for complete remission were multiple versus single perfusion schedule, the absence of regional node involvement, and leg versus other tumor sites. The 3-year limb recurrence-free interval was 38%. Factors associated with this interval were one as opposed to more than one lesion, complete remission after perfusion, and female sex. Patients exhibiting complete remission after perfusion had a better overall 3-year survival rate than had patients without complete remission (60% vs 35%; p = 0.0012). CONCLUSIONS: In the present study prognostic factors for tumor response and limb recurrence-free interval could be determined. A multiple perfusion schedule may be more effective in providing complete remission in patients undergoing regional isolated perfusion than single perfusions are.

Adult↗
PubMed1993

Drug-induced DNA modification in buccal cells of cancer patients receiving carboplatin and cisplatin combination chemotherapy, as determined by an immunocytochemical method: interindividual variation and correlation with disease response.

Twenty-six patients with a variety of tumor types were treated according to a phase 1 experimental treatment protocol consisting of repetitive cycles of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin, 200-480 mg/m2) at day 1 and cis-diamminedichloroplatinum(II) (cisplatin, 50-100 mg/m2) at day 3. Buccal cells were collected in one or two treatment cycles prior to carboplatin, 24 h after carboplatin, just prior to cisplatin, and approximately 24 h after cisplatin administration. Drug-induced DNA modification was visualized at the single cell level by anti-serum NKI-A59 and quantitated by microdensitometry. All (39 of 39) treatments with carboplatin, and almost all (33 of 35) treatments with cisplatin resulted in an increase in nuclear stain. Interindividual variation in drug-induced, adduct-specific nuclear stain amounted to a factor of 5-8 for carboplatin and 5-12 for cisplatin. This drug-induced increase was, however, not related to the dose of either carboplatin or cisplatin, suggesting that large interindividual differences in DNA adduct formation and/or repair obscured the effects of dose variation within the relatively small range used for the drugs (2.4 for carboplatin and 2.0 for cisplatin). This explanation was strengthened by the good reproducibility of the immunocytochemical assay and by the reasonable correlation between carboplatin-induced nuclear stain in cycles 1 and 2 (correlation coefficient, 0.69; P = 0.009). Mean carboplatin-induced nuclear stain was significantly higher in the first cycle than in the second cycle (P = 0.0001) but this difference was no longer significant when drug-induced nuclear stain was corrected for carboplatin dose. Differences in cisplatin-induced nuclear stain between cycle 1 and cycle 2 were small and not significant. Carboplatin-induced nuclear stain was significantly higher in the partial responders than in the nonresponders (P < 0.0001, two cycles combined); the level of statistical significance remained the same after dose correction. Cisplatin-induced nuclear stain did not differ significantly between partial responders and nonresponders; this result might, however, be confounded to some extent by remaining carboplatin-induced nuclear stain at the moment of cisplatin administration. It is concluded that determination of the extent of platinum-induced DNA modification might be helpful in predicting the tumor response in cancer patients.

Adult↗