Biomedical subjects

D Harms

Publications and source records attributed to D Harms.

At least 109 records · Page 6Linked to original sources

PubMed1993

DNA analysis in hepatoblastoma by flow and image cytometry.

BACKGROUND: In several types of tumors, including hepatocellular carcinoma, prognosis could be correlated with DNA ploidy. Few studies have been performed on hepatoblastoma with contradictory results. METHODS: Twenty-nine cases of nonpretreated hepatoblastoma were studied with flow cytometry and image cytometry for DNA index and proliferation index using paraffin-embedded tissue. RESULTS: Twenty-three (79.9%) tumors were diploid, and 6 (20.7%) were aneuploid (hyperdiploid). Patients with diploid tumors were younger than those with aneuploid tumors. With regard to stage, diploid tumors were almost equally distributed among stages (tumor, lymph node metastases, distant metastases), whereas aneuploid tumors tended to occur in higher stages (tumor, lymph node metastases, distant metastases). Diploid tumors had clearly a better prognosis than aneuploid tumors, although the difference was not statistically significant (flow cytometry, P = 0.06; image cytometry, P = 0.16). A more favorable prognosis was also noted for hepatoblastomas with low-proliferation index (< or = 7%), but the difference from tumors with high-proliferation index (> 7%) again was not statistically significant (P = 0.16). CONCLUSIONS: Although no statistically significant differences in prognosis between hepatoblastomas with diploid and aneuploid DNA content, respectively, were found, there is a clear tendency that diploid hepatoblastomas behave more favorably. The same is true for hepatoblastomas with low-proliferation index.

Aneuploidy↗

PubMed1993

Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification.

Mutation of the p53 tumor suppressor gene frequently occurs in a variety of tumors including lung, breast, gastrointestinal, and brain, as well as lymphomas-leukemias. Neuroblastoma, one of the most common solid tumors in childhood, often has amplification of the N-myc gene. We examined for mutations of the p53 tumor suppressor gene by single-strand conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assessed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, two mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation was located in exon 5, and another was in exon 6. N-myc gene was amplified in 26% of the samples. No p53 mutations were found in neuroblastoma samples with N-myc amplification. In the two individuals, p53 mutations appeared as their disease became more progressive. The neurofibromatosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spot of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were unable to detect an abnormality in this region of NF1 in 50 samples of neuroblastoma. The data suggest that p53 mutations occasionally are associated with progression of neuroblastomas, and tumorigenetic influences of mutant p53 may differ from those of N-myc.

Gene Amplification↗

PubMed1993

Rare tumors in childhood: pathological aspects. Experience of the Kiel Pediatric Tumor Registry.

A wide variety of rare tumors can occur in childhood and adolescence. Tumors can be rare in any age group; common tumors of adults can appear in childhood and adolescence, and many rare tumors and tumor-like lesions show a predilection for younger age groups. Comparatively frequent tumors can present with rare histologic features or can occur in rare atypical locations, and, finally, seemingly common but, in fact, rare tumors have to be distinguished from truly common but rarely recognized tumors. Thus, the spectrum of rare tumors is broad, reflecting the fluent reality of life.

Adolescent↗

PubMed1993

Rhabdomyosarcomas with primary presentation in the skin.

Five primary and two metastatic rhabdomyosarcomas (RMS) with primary presentation in the skin were studied by conventional light microscopy and immunohistochemistry. These cases account for only 0.7% of the 682 cases of RMS collected at two large institutions with a main interest in soft tissue tumors. All but one tumor, which was an embryonal RMS, corresponded to the alveolar subtype. The myogenic nature of the tumor cells was supported by the immunophenotype including positive reactions for vimentin, desmin, and muscle actin. Clinical findings included a male predominance, young age of the patients and the location of all primary cutaneous RMS in the face. One of the two metastatic RMS presented at birth with a clinical picture highly suggestive of congenital metastatic neuroblastoma, notably because of a 100-fold amplification of the N-myc copy number. Thus, this case illustrates again that an amplification of the N-myc oncogene is not restricted to neuroblastoma, but may also occur in other tumor types.

Child↗

PubMed1993

Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region. A report of the Intergroup Rhabdomyosarcoma Study.

We reviewed 173 cases of paratesticular rhabdomyosarcoma (RMS) of Intergroup Rhabdomyosarcoma Studies (IRS)-I, -II, and -III for evaluation of possible histological factors that might account for the good prognosis of these patients. Almost all cases (161 of 173 cases, 93.1%) occurring in this site were of embryonal histology. A spindle-cell subtype of embryonal RMS was identified that presented a storiform growth pattern with abundant collagen between the tumor cells in most cases. Other tumors of this subtype showed an arrangement of tumor cells in bundles with a low to moderate amount of collagen, resembling a leiomyosarcoma. The other embryonal RMS in this site had the classical embryonal cytology. The spindle-cell subtype was highly differentiated by immunohistochemistry and electron microscopy. Lymph node metastasis was found in seven of 43 patients (16.3%) with a RMS of spindle-cell subtype, compared with 40 of 112 patients (35.7%) with RMS of non-spindle-cell type. Clinical data from patients with spindle-cell subtypes of the paratesticular lesions revealed that they almost always had an association with clinical groups of limited disease (32 patients, 74.4%, with Group I; 10 patients, 23.3%, with Group II disease) and a significantly better prognosis (95.5% survival at 5 years) when compared with patients with the classic embryonal variant of RMS (80% survival at 5 years, p < 0.035). The incidence and anatomic distribution of this spindle cell subtype of embryonal RMS was estimated on 800 randomly selected patients from IRS-II. It was found in the head and neck, extremities, orbit, and some other sites, but 30.6% were located in the paratesticular area. Patients with spindle cell RMS of nonparatesticular sites usually had more extensive disease compared with patients having paratesticular lesions; two thirds of the cases had gross residual tumor after surgery or metastatic tumor at diagnosis. We conclude that spindle-cell RMS is a subtype of embryonal RMS with a very favorable prognosis. The site factor of the paratesticular localization may allow earlier diagnosis of the spindle-cell lesions compared with other sites. Other unknown factors may also play a role.

Child↗

PubMed1993

Discrimination between immunoaccessory and phagocytic monocytes/macrophages of the skin in paraffin-embedded tissue by the monoclonal antibody Ki-M1P.

The variety of functions performed by monocytes and macrophages is reflected in their phenotypic diversity. Investigation of this complex system is facilitated by Ki-M1P, a new monoclonal antibody which recognizes a differentiation antigen on monocytes/macrophages in paraffin-embedded tissues. To test its usefulness as a pan-macrophage marker in the skin, we immunohistochemically analysed paraffin-embedded biopsy material from seven healthy individuals and 190 patients with a variety of dermatoses. Immunoreactivity was compared with results obtained with the antibodies KP-1, MAC-387, UCHL-1 and S-100. In normal skin, epidermal Langerhans cells were Ki-M1P-. Strong expression of this marker was detected on spindle-shaped as well as dendritic perivascular and intervascular macrophages. Pathological reaction forms such as giant cells and epithelioid cells in granulomatous dermatoses were also Ki-M1P+. The high specificity of Ki-M1P is reflected in the lack of reactivity with tumour cells in non-monocytic neoplasms and Langerhans cell histiocytosis. Thus, Ki-M1P is a useful marker for skin macrophages, discriminating between the immunoaccessory and the phagocytic compartments.

Antibodies, Monoclonal↗

PubMed1993

Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury.

In organ repair following injury, macrophages accumulate and granulation tissue, comprised of fibroblasts and endothelial cells, develops in the injured area. Basic fibroblast growth factor (bFGF), a potent stimulator of fibroblast and endothelial cell growth, has been linked to the fibroproliferative process. Macrophages are thought to play a central role in the fibroproliferative response, and prior studies indicate that they produce bFGF. Whereas it is plausible that macrophages produce bFGF in a fibroproliferative process, currently no data exists that directly identifies the macrophage as a source of bFGF in a fibroproliferative disorder. We used the model of acute intraalveolar granulation tissue formation following lung injury to determine if the macrophage was a cellular source of bFGF in a naturally occurring fibroproliferative process. To examine this hypothesis, patients with severe acute lung injury underwent bronchoalveolar lavage during the phase of lung repair. Polymerase chain reaction and Northern analysis of macrophage RNA revealed the presence of two species of bFGF messenger RNA (4.4 kb and 1.9 kb). Metabolic labeling studies of recovered macrophages revealed a newly synthesized 18-kd protein with antigenic similarity to bFGF. Immunohistochemical evaluation of lung tissue from patients who died following acute lung injury, showed numerous bFGF immunoreactive macrophages present within airspaces containing fibroblastic and vascular tissue proliferation. This investigation has identified the alveolar macrophage as a cellular source of bFGF in the fibroproliferative disorder of intraalveolar fibrosis following acute lung injury.

Autoradiography↗

PubMed1992

Malignant rhabdoid tumor: primary intracranial manifestation in an adult.

Clinical, histopathological, and ultrastructural features of an extended intracranial malignant neoplasm are presented. Following incomplete extirpation of a large epidural tumor at the temporal base of the skull, the 21-year-old male patient suffered from several local recurrences and died at the age of 27. The neoplasm was defined by its histopathological and ultrastructural characteristics and by the pattern of its antigenicity as a malignant rhabdoid tumor (MRT). Considering previous publications on MRT, this case may be the first of primary intracranial MRT appearing in an adult.

Adult↗

PubMed1992

Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma.

In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.

Biomarkers, Tumor↗

PubMed1992

Malignant renal tumors of childhood.

The prognosis in nephroblastoma (Wilms' tumor) has been improved considerably by treatment protocols combining surgery, chemotherapy, radiation therapy, and, in some clinical trials, pre-operative chemotherapy. Cure is now achieved in most patients. All clinical trials have employed treatment strategies tailored to the individual risk of the patient, including the histological subtype of the tumor. In the National Wilms' Tumor Study (NWTS) of the United States these subtypes have been divided into two groups of tumors according to their "favorable" or "unfavorable" histology. At the Kiel Pediatric Tumor Registry we have devised a system which distinguishes three groups of tumors classified according to prognosis. The first group includes tumors with a favorable prognosis, even if only surgery is performed. These comprise congenital mesoblastic nephroma (CMN) and cystic, partially differentiated nephroblastoma (CPDN). The second group consists of tumors posing an intermediate risk, such as typical nephroblastoma and its histological variants characterized by variations in the relative proportions of the histological components. Fetal rhabdomyomatous nephroblastoma (FRN) is also included in this group. The third group comprises tumors of high risk such as anaplastic nephroblastoma, clear cell sarcoma of the kidney (CCSK), and malignant rhabdoid tumor of the kidney (MRTK). Since histological diagnosis plays a crucial role in the assignment of a patient to a particular type of treatment protocol, knowledge of the histological appearance of the various tumor types both with and without preoperative treatment is of utmost importance.

Antineoplastic Agents↗

PubMed1992

Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma.

Twenty-one cases of embryonal rhabdomyosarcoma, composed mainly of elongated spindle cells arranged in a fasciculated or storiform pattern, were retrieved from the files of the German-Italian Cooperative Soft Tissue Sarcoma Study. The term spindle cell rhabdomyosarcoma is proposed to designate this histotype. Spindle cell rhabdomyosarcoma predilected male patients (18 males, three females) and involved mostly the paratesticular area (12 cases) and the head and neck region (six cases). Histologically, all cases were characterized by a uniform proliferation of elongated spindle cells with eosinophilic and fibrillar cytoplasm mimicking smooth muscle fibers; immunocytochemical studies disclosed high expression of the muscle markers titin, desmin, and myoglobin. Clinical information was available in 17 cases; according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, 13 were classified in group I, two in group II, and two in group III. Sixteen patients were well and alive 24 to 100 months after diagnosis; one patient died from disease progression 24 months after diagnosis. Analysis of our results determined that spindle cell rhabdomyosarcoma constitutes a rare variant of the embryonal form, showing a high degree of skeletal muscle differentiation and a low malignant potential; it should therefore be distinguished from classical forms of embryonal rhabdomyosarcoma.

Adolescent↗

PubMed1992

Infectious risks of Broviac catheters in children with neoplastic diseases: a matched pairs analysis.

In the present study the complication rate of Broviac catheters in the therapy of children with cancer was determined. Of special interest was the question of to what extent the incidence of bacteremias is increased by the implant. For this reason the method of matched pairs analysis was chosen comparing 55 patients with 61 catheters to 1 child each who received the therapy via peripheral veins. Apart from having the same disease, the same therapy protocol and the same age group the partners had a similar number of leukocytopenic days (leukocyte counts, < 1000/microliters) in the study period. The observation time was 9671 days in the catheter group and 9666 days in the control group. During this time 167 fever episodes (17.7 episodes/1000 days) were recorded in the patients with implant but only 133 episodes (14.0/1000 days) in the control patients. Study and control groups had similar frequencies of fever of unknown origin with leukocyte counts > or = 1000/microliters and fever with a known focus. However, 29 bacteremias (2.9 episodes/1000 days) represented a 4 times higher complication rate with the use of Broviac catheters than in the control group (7 bacteremias, 0.7 episode/1000 days). Episodes of fever of unknown origin with leukocytopenia were 1.5 times more common in the catheter group than in the control group. Although it is not possible to prove that the catheter played a role as focus of bacterial infection, an increased risk of infection must be supposed. The Broviac catheter meets with broad approval by the patients, parents and medical staff.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteremia↗

PubMed1992

[Experiences with surfactant therapy of adult respiratory distress syndrome].

We report on 2 patients with ARDS, who underwent a therapy with surfactant. In both cases the underlying reason for the lung disease probably was a viral pneumonia. In both patients the gas exchange improved after tracheal instillation of surfactant. This improvement however was much less than we know it from therapy of the respiratory distress syndrome of the premature babies. Reasons for these differences in response to surfactant are discussed.

Child, Preschool↗

PubMed1991

Malignant peripheral neuroectodermal tumor and its necessary distinction from Ewing's sarcoma. A report from the Kiel Pediatric Tumor Registry.

A new classification scheme is proposed for the differential diagnosis of Ewing's sarcoma and malignant peripheral neuroectodermal tumor (MPNT) based on conventional light microscopic and immunohistochemical findings. The presence of Homer-Wright rosettes and/or the expression of at least two neural markers is diagnostic of MPNT Ewing's sarcoma. Ewing's sarcoma was diagnosed in cases lacking Homer-Wright rosettes and expressing no neural marker or only one in immunohistochemistry. Using this "new" approach considerable differences were found between both tumor types. Although most MPNT were located in the thoracopulmonary region, Ewing's sarcoma was located predominantly in the pelvis and extremities. The mean age of MPNT patients was greater than that of Ewing's sarcoma patients. Most importantly, however, was a statistically significant difference in prognosis: disease-free survival in Ewing's sarcoma patients at 7.5 years follow-up was 60% compared with 45% MPNT patients (P = 0.026). The detection of HNK-1 in MPNT indicated a more aggressive biologic behavior, and the expression of protein S-100 appeared to be correlated with a more favorable clinical course.

Adolescent↗

PubMed1991

Synovial sarcoma in children and adolescents. A report from the Kiel Pediatric Tumor Registry.

Of 49 cases of synovial sarcoma, which represent 5.8% of all soft tissue sarcomas with confirmed diagnosis in the files of the Kiel Pediatric Tumor Registry (Kiel, Germany), 35 occurred in patients up to the age of 18 years. The lower extremities were the most common. The 35 cases included 21 biphasic and 14 monophasic fibrous synovial sarcomas. The different cell types constituting synovial sarcoma could be demonstrated by conventional light microscopic study, but more readily so by immunohistochemical study, particularly when antibodies against cytoskeletal components were applied. Aberrant antigen expression was noticed for the neural markers, protein S-100, and neuron-specific enolase. Moreover, four tumors were positive for Ki M7. Collagen type IV was found in all tumors tested. For the 20 patients enrolled in the Cooperative Soft Tissue Sarcoma Study of the German Society of Pediatric Oncology (GPO) the survival rate at 7 years is 63%. When five patients with initial recurrence are excluded, the survival rate is 72%. It is concluded that immunohistochemical study is useful in the diagnosis and differential diagnosis of synovial sarcomas despite certain limitations. Multimodality treatment approach has improved the overall prognosis. There is no relationship between histologic subtype and prognosis according to the classification scheme employed in this study.

Adolescent↗

PubMed1991

Determination of the anatomical size of ventricular septal defects on the basis of hemodynamic data and noninvasive assessment of pulmonary to systemic vascular resistance ratio Rp/Rs by Doppler-echocardiography.

The pulmonary and systemic flow (Qp/Qs) and resistance ratios (RP/Rs) were determined in children with isolated ventricular septal defects (VSD) to derive an "effective defect resistance" (Rd/Rs) representing the ratios of the resistance of the defect to the systemic vascular resistance. The defect size (expressed as the ratio of the area of the defect to the cross-sectional area of the ascending aorta) was related to the calculated "effective defect resistance," where a significant (non-linear) correlation was found. The effective resistance of the defect is a useful aid for estimation of the anatomical size of a ventricular septal defect. The close correlation between anatomical size and the hemodynamic parameter Rd/Rs allows one to calculate the ratio Rp/Rs with this concept using noninvasive Doppler-ultrasound and echocardiography. This was performed in 21 children with VSD who underwent cardiac catheterisation. The noninvasive calculated flow ratio Qp/Qs and the resistance ratio Rp/Rs showed a close correlation to the values measured at cardiac catheterisation.

Cardiac Catheterization↗

PubMed1991

Renal cell carcinoma in children: histology, immunohistochemistry, and follow-up of 10 cases.

Ten renal cell carcinomas in children under 15 years were investigated. The average age was 122.5 months and the girls predominated in our cases (7 girls, 3 boys). By using the classification of Thoenes et al., Pathol Res Pract 181: 125-143, 1986 a predominance of clear cell-eosinophilic tumor cell type and of the tubulopapillary growth pattern was found. Immunohistochemistry revealed a heterogeneity of cytokeratin expression. By using the monoclonal antibodies Cam 5.2 and KL 1, cytokeratins were found in 7 cases each. The other 4 cytokeratin antibodies used were less sensitive. The expression of cytokeratin 13 in 3 cases suggested a more complex histogenesis than assumed. Vimentin was found in 3 tumors, but an association to a higher grade (G) of malignancy was not found in these cases. One tumor expressed the Tamm-Horsfall-protein, which is predominantly found in the distal tubule of the normal kidney. In summary the results of immunohistochemistry characterized the great heterogeneity of these tumors. Follow-up information was available in 9 cases. All patients with G I- and G II-tumors were free of disease after an average time of 39.6 months (mean 27 months). Two of the 3 cases with G III-tumors died after 9 and 15 months, despite additional chemo- or radiotherapy. Therefore tumors of grade I and II of the Thoenes classification seem to have a good prognosis.

Adenocarcinoma↗

PubMed1991

Infantile desmoid-type fibromatosis. Morphological features correlate with biological behaviour.

It is generally agreed that the biological behaviour of infantile desmoid-type fibromatosis is unpredictable in terms of the likelihood of local recurrence. We evaluated the prognostic importance of the number of slit-like blood vessels with a mean diameter of less than 20 microns and of the quantity of undifferentiated mesenchymal cells. In addition, we studied the immunophenotypic characteristics of the proliferating cells and their nucleolar organizer region (AgNOR) numbers and distribution. Statistical analysis showed that the tendency to recur locally was correlated with larger numbers of slit-like blood vessels and undifferentiated mesenchymal cells. The proliferating cells were identified by immunohistochemistry as myofibroblasts. No correlation was found between AgNOR numbers and clinical course of the disease. We conclude that histological features easily evaluated by conventional light microscopy provide useful information on the possible course of infantile desmoid-type fibromatosis.

Actins↗