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R Kolb

Publications and source records attributed to R Kolb.

At least 19 recordsLinked to original sources
PubMed2004

CNS disease as the main manifestation of hemophagocytic lymphohistiocytosis in two children.

Hemophagocytic lymphohistiocytosis is a rare and fatal disorder of early infancy, which affects predominantly the mononuclear phagocyte system and is characterized by the presence of fever, hepatosplenomegaly and cytopenia. Neurological symptoms can be extremely variable, ranging from irritability, and convulsions to focal neurological signs. They often develop during disease progression, but can also be the leading initial symptoms. Early diagnosis is mandatory, because new treatments, including bone marrow transplantation, appear to be promising. Here we present the clinical, neuroradiological and histopathological findings from two children with progressive CNS disease as the main clinical manifestation of hemophagocytic lymphohistiocytosis. Both children died and diagnosis was only obtained in retrospect after careful review of the histopathological material.

Central Nervous System Diseases↗
PubMed2003

Volumetric bone mineral density in patients with childhood craniopharyngioma.

As the overall survival rate is high in patients with craniopharyngioma, the prognosis in survivors depends mainly on late effects. Late effects such as hypogonadism, growth hormone deficiency, glucocorticoid overreplacement and obesity have a strong impact on volumetric bone mineral density (vBMD). We analyzed vBMD and possible risk factors for reduced vBMD in 61 patients with childhood craniopharyngioma (29 f; 32 m) and in 14 weight, age, and sex-matched controls. VBMD was quantified by peripheral quantitative computed tomography (pQCT). Endocrine status, hormonal substitution therapy and calcium phosphate metabolism were evaluated. VBMD was in the lower normal range in 61 craniopharyngioma patients (total radial z-scores: median - 1.5; range - 3.1 to 1.4; trabecular z-scores: median - 0.4; - 2.4 to 2.3). 23 severely obese patients (body mass index [BMI] > 4 SD) had a higher total radial (p < 0.05) and trabecular (p < 0.05) vBMD when compared with 38 non-severely obese patients and 7 weight-matched controls. Although there was no gender difference in terms of obesity, endocrine substitution therapy or calcium phosphate metabolism, male patients had lower total radial (p < 0.01) and trabecular (p < 0.05) vBMD. Only in male patients' vBMD z-scores showed a positive correlation with BMI standard deviation score (SDS) (total radial z-score: Spearman r = 0.38, p = 0.03; trabecular z-score: Spearman r = 0.35, p = 0.04). We conclude that obesity has a major impact on vBMD in patients with craniopharyngioma. Lean male patients are at special risk for a lower vBMD, whereas female gender and severe obesity seem to have a protective effect regarding vBMD.

Adolescent↗
PubMed2003

Perioperative dexamethasone treatment in childhood craniopharyngioma--influence on short-term and long-term weight gain.

The substitution of dexamethasone during and after surgery of childhood craniopharyngioma is necessary in order to treat and/or prevent brain edema and adrenal insufficiency. Early post-operative weight gain is a predictor for severe obesity during long-term follow-up. In a retrospective analysis of 60 patients with childhood craniopharyngioma we inquired whether dose and duration of perioperative dexamethasone therapy (n = 68) had influence on short-term post-operative weight gain and long-term development of severe obesity. The median follow-up period was 4.2 years, ranging from 1 to 9 years. 24 patients (14 f/10 m) developed severe obesity (BMI > 3 SD). 28 patients (10 f/18 m) retained normal weight (BMI < 2 SD). Eight patients presented with a BMI between 2 and 3 SD at the final visit. Differences in terms of age at surgery or follow-up period were non-detectable between the analyzed groups of craniopharyngioma patients. Duration and cumulative dexamethasone doses (mg/m2 BSA) for perioperative dexamethasone therapy were similar for severely obese patients (duration: 8.7 d; 4.5 - 17 d, cumulative dose: 74; 42 - 177 mg/m2 BSA) and normal weight patients (duration: 10.0 d; 1 - 41 d; dose: 76; 9 - 390 mg/m2 BSA). Whereas cumulative dexamethasone doses positively (p < 0.01; rho: 0.424) correlated with weight gain during the first year following surgery, long-term development of severe obesity was not influenced by dose and duration of perioperative dexamethasone treatment. Patients who developed severe obesity during follow-up had a higher (p < 0.001) BMI already at the time of diagnosis. We conclude that dose and duration of perioperative dexamethasone treatment had short-term effects on post-operative weight gain, but not on the development of long-term severe obesity. The results of our retrospective analysis are currently tested in a prospective surveillance study Kraniopharyngeom 2000 (www.kraniopharyngeom.com).

Adolescent↗
PubMed2003

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: the dominant role of DHI.

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Biopsy↗
PubMed2000

Somatizing patients: part II. Practical management.

Somatization is the experiencing of physical symptoms in response to emotional distress. It is a common and costly disorder that is frustrating to patients and physicians. Successful treatment of somatization requires giving an acceptable explanation of the symptoms to the patient, avoiding unwarranted interventions and arranging brief but regular office visits so that the patient does not need to develop new symptoms in order to receive medical attention. Antidepressants may be helpful in many patients, as well as cognitive psychotherapy when patients are willing to participate in it. Typical problems in managing such patients can be addressed by relying on the continuity established through regular visits to the same primary care physician.

Diagnosis, Differential↗
PubMed2000

[Bone manifestations in non-Hodgkin's lymphoma in childhood and adolescence].

PURPOSE: Skeletal manifestation of Non-Hodgkin's lymphoma is rare in pediatric patients. Objective of the study was to determine imaging features, before and after treatment, and to correlate these features with clinical outcome. METHODS: A retrospective analysis of 1246 patients from two therapy studies (NHL-BMF-90 and 95) was performed. Imaging studies of 63 patients with bone involvement of lymphoma were reevaluated. RESULTS: Incidence of initial bone involvement in Non-Hodgkin's lymphoma was 6.8%. Distribution was best assessed by bone scan, MRI revealed larger areas of marrow involvement and detected additional lesions. Sites of predilection were long bones of the lower extremities with epiphyseal involvement in 39%. Residual signal alterations in MRI after successful therapy remained in 71%. Osteonecrosis after therapy was a common finding. Clinical outcome war not correlated to the presence of bone involvement. CONCLUSIONS: Since clinical outcome is not effected by bone involvement in childhood NHL, value of screening may be limited. Knowledge of imaging characteristics is mandatory for initial evaluation of primary osseous lymphomas and symptomatic lesions as well as for therapy controls.

Adolescent↗
PubMed2000

[Primary epithelioid angiosarcoma of the proximal trachea].

A 81-year-old man presented with massive hemoptysis and dyspnea. Results of chest radiography and computer tomography were highly suspicious for a large right-sided tumor of the bronchus with impression of the right main bronchus. Because of clinical worsening the patient was transferred to our department of pulmonology. The patient died of unappeasable hemoptysis the next day. At autopsy we found a 2-cm-diameter tumor of the proximal trachea as the source of massive bleeding and blood aspiration. Histological examination confirmed the tumor to be an epithelioid angiosarcoma of the trachea, which was a primary as no other tumor manifestation was detected. The entity of epithelioid angiosarcoma as a primary tumor of the trachea, to our knowledge, has not yet been reported.

Aged↗
PubMed1999

The somatizing patient.

Somatization is the experience of physical symptoms in response to emotional distress. It is common, costly, and frustrating to both the patient and physician. Successful treatment of somatization requires the physician to pursue a positive diagnosis rather than rely on a diagnosis of exclusion. Treatment consists of giving an acceptable explanation of the symptoms to the patient, avoiding unwarranted interventions, and arranging brief but regular office visits for which the patient does not need to develop a new symptom to receive medical attention.

Diagnosis, Differential↗
PubMed1999

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Age Factors↗
PubMed1998

A new semiautomated, three-dimensional technique allowing precise quantification of total and regional cerebellar volume using MRI.

A new method was developed to measure total and regional cerebellar volumes using MRI. Previously, the volumes of the cerebellum and its substructure had been studied planimetrically. The new method uses three-dimensional semiautomated volumetry with focus on reliability and performance. The method consists of a manual presegmentation using landmark-adjusted planes followed by region-growing segmentation and calculation of volume. The cerebellum is partitioned into 11 regions defined by planes, which are adjusted for internal cerebellar landmarks (three radial regions inside the vermis that extend into the medial hemisphere (one-fourth of the transverse diameter of the hemisphere); one region in the lateral hemisphere (remaining three-fourths)). Forty-six healthy volunteers were examined and the effects of age, gender, and symmetry were estimated. Shrinkage in the vermis (especially anterior superior compartment) was marked. Age effects diminished laterally and were not observed in the lateral hemisphere. Age effects on the total cerebellar volume were marginal. Effects of gender and symmetry were nonsignificant. Technique and results are discussed and related to methods and findings of others.

Adult↗
PubMed1998

Lesion location influences perception of homonymous scotomata during flickering random dot pattern stimulation.

An attempt was made to clarify whether the site of postchiasmal lesions affects subjective perception of homonymous visual field defects during stimulation with flickering random dot patterns (white noise-field). Out of 56 patients with homonymous hemianopia, 38 (68%) perceived scotomata in this situation, but 18 (32%) discerned none at all. Neuroradiologic superposition of cerebral lesions detected by computed tomography (CT) or magnetic resonance imaging (MRI) showed that nearly all patients who perceived their scotomata had lesions involving the primary visual cortex or the perigeniculate region, whereas those who received no scotoma had lesions centered within the optic radiation. Functional MRI of six normal subjects during stimulation with flickering random dot patterns indicated predominant activation of the primary visual cortex. Since noise-field defects were most frequently perceived by patients whose lesion involved the primary visual cortex, it appears that the sensitivity of noise-field campimetry depends on the site of damage in the visual pathway. The explanation for this may be that damage to long-range horizontal connections impairs filling-in processes.

Adolescent↗
PubMed1998

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

Adult↗
PubMed1996

Menstrual phase and breast cancer surgery: influence on clinical outcome or pitfall of statistical analysis?

The influence of menstrual status at the time of surgery on the prognosis of women suffering from breast cancer is still discussed controversially. In our patient collective, including 149 patients, we obtained statistically significant results for six different time intervals, indicating that patients who underwent surgery between 11 and 22 days after the last menstrual period (LMP) have a poorer outcome. Focusing on the effect of statistical data evaluation strategy we designed a simulation study to evaluate the amount of type I error (error of a false positive test result) in a multiple testing situation involving a cyclical covariate. Accordingly, we corrected the minimum P-values for the occurring type I error rates. After that correction all six previously significant P-values failed to achieve statistical significance. The impact of different statistical data evaluation strategies in a multiple testing situation is discussed.

Adult↗
PubMed1996

The Xmrk oncogene promoter is derived from a novel amplified locus of unusual organization.

Hereditary melanoma in Xiphophorus hybrids is caused by the receptor tyrosine kinase Xmrk. Tumor formation is initiated by overexpression of the Xmrk gene, apparently because of insufficient transcriptional control in the melanocytic lineage of hybrid fish. The oncogenic Xmrk resulted from gene duplication and nonhomologous recombination of the corresponding Xmrk proto-oncogene during evolution. By this event Xmrk was translocated downstream of the promoter of another gene, D (for Donor). This raised the question whether both the Xmrk oncogene and D share similar transcriptional control elements. Studies on the genomic organization of D showed that this gene is amplified in the Xiphophorus genome, presumably with all copies clustered on a single chromosome. Surprisingly, at least two completely different, tightly linked genes are included in the amplified segment. We find a ubiquitously expressed zinc finger gene of the krüppel type, followed by a previously unknown gene, which was the partner of the Xmrk proto-oncogene in the recombination generating the Xmrk oncogene. The nucleotide sequence predicts a gene product with very high amino acid similarity to a hypothetical Caenorhabditis elegans protein. The expression pattern is unrelated to that of the Xmrk oncogene suggesting that despite extended sequence homology a new type of promoter was created by this rearrangement.

Amino Acid Sequence↗
PubMed1996

Cerebral activity during visual stimulation: a positron emission tomography and functional magnetic resonance imaging study.

Stimulation of cerebral areas induces a regional increase in blood flow and metabolism. Positron emission tomography (PET) is an established procedure to localize cerebral regions of enhanced activity. Exposure to a radioactive indicator and limited spatial and temporal resolution are disadvantages of this method as compared with other imaging techniques, but anatomical orientation can be improved by matching PET images with high-resolution magnetic resonance imaging (MRI) scans. Recently, functional MRI (fMRI) has arisen as an alternative method. This procedure presumably detects changes in the paramagnetic properties of hemoglobin, depending on its oxygenation state, as well as an increased regional blood flow in activated cerebral areas. These structures can be visualized using sensitive scanning techniques and appear with bright signal intensities. Visual stimulation was performed with the help of a high-resolution color VDU for PET registration and of an LCD video projector for fMRI (1.5 T). Hemifield stimulation as well as subtraction between images of flickering and stable random dot stimuli showed a preferential activation of the primary visual cortex. In addition, the first MRI results obtained during stimulation with moving gratings are demonstrated; hereby, preferentially extrastriate regions presumably responsible for motion detection were activated.

Adult↗
PubMed1995

Scotoma perception in white-noise-field campimetry and postchiasmal visual pathway lesions.

The authors examined 59 patients (32 women and 27 men) suffering from homonymous hemianopia by white-noise-field campimetry (Tübingen Electronic Campimeter) and by conventional perimetry (Tübingen Automatic Perimeter or Tübingen Manual Perimeter) and by computerized tomography (CT) or magnetic resonance imaging (MR). In all, 56 patients showed neuroradiologically detectable cerebral lesions, which were superimposed in a reconstructed "reference brain". Of these 56 patients, 18 were not capable of perceiving any white-noise-field scotoma, although their conventional perimetric findings showed defects. Lesions of these patients were concentrated along the optic radiation and spared the primary visual cortex. The lesions of the remaining 38 patients with scotoma detectable in both methods were accumulated in area V1, the primary visual cortex. The lesions of 6 patients, who had had persistent scotoma perception for more than 2 years, were situated at the occipital pole. The lesions of 8 patients with vanishing scotoma were concentrated in more rostral areas.

Adolescent↗