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Biomedical subjects

L Buhl

Publications and source records attributed to L Buhl.

At least 19 recordsLinked to original sources

Cerebral oedema as a possible complication of treatment with imatinib.

Imatinib is a potent drug used in treatment of chronic myeloid leukaemia (CML). It acts by inhibition of the CML-specific p210 BCR-ABL tyrosine kinase, but also blocks other pathways such as platelet-derived growth factor (PDGF) and c-kit receptor signalling. Clinical trials have confirmed the efficacy of imatinib, which has toxic effects in cells that express BCR-ABL. Side-effects, although frequent, are generally mild and include superficial oedema and fluid retention. Here, we describe two patients with cerebral oedema, which in one patient was fatal. The pathophysiological mechanisms remain unknown, although the drug could act through inhibition of the PDGF receptor.

Aged↗

Surface immunoglobulin on B lymphocytes as a potential target for specific peptide ligands in chronic lymphocytic leukaemia.

With the aim of producing unique targets for malignant cells we have identified peptide ligands for the clonal surface immunoglobulin isolated from the B cells of a chronic lymphocytic leukaemia (CLL) patient. The peptides were identified from random-peptide phage-display libraries. The obtained ligands bound specifically to the surface of the target lymphocytes as well as to clonal immunoglobulin in lysate from the same cells. Peptide-based antigen mimotopes may have a future use in targeted therapy of CLL and other B-cell-derived malignancies displaying surface immunoglobulin.

Amino Acid Sequence↗

Identification of patient-specific peptides for detection of M-proteins and myeloma cells.

We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M-proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage-displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.

Adult↗

Epidemiology and prognosis in children treated for intracranial tumours in Denmark 1960-1984.

A total of 911 Danish children under 15 years of age were treated for an intracranial tumour in the 25-five year period 1960-1984. All cases were followed up to the end of 1994 or to emigration or death if one of these came sooner. The mean annual incidence was 32.5 per million children with a slight increase over the 25 years. The male/female ratio was 1.15 and close to the M/F ratio for the entire Danish population of children. Of the tumours, 46% were located in the supratentorial and 54% in the infratentorial compartment, and 94% were verified histologically. In order of frequency the most common types were astrocytomas (all grades, 35%), medulloblastomas (20%), ependymomas (14%), and craniopharyngiomas (5%). Total removal of the tumour was performed in 277 and partial removal, including biopsy, in 490 children. In 57 patients a shunt operation only was performed, and 87 children did not have an operation or died before the correct diagnosis was established. Radiotherapy was administered in 55%. The outcome depended on extent of removal, radiation, location and histology of the tumour. Most (784 or 86%) of the children survived more than 1 month after diagnosis or operation, and 353 children (39% of the whole series, 47% of those alive more than 1 month after diagnosis) were alive at follow-up. Of the survivors 29% had a tumour in the supratentorial midline, 26% one in the lateral part of the supratentorial area, 31% a cerebellar tumour and 13% a IV ventricle tumour. It was possible for 66% of the survivors with supratentorial and 90% of those with infratentorial tumours to lead a normal life. The long-term prognosis was especially good for children with cerebellar and supratentorial astrocytomas and optic chiasma tumours. Children with juvenile cerebellar astrocytoma had the best prognosis: 90% were alive at the end of the follow-up period, as against 20% of those with medulloblastoma and 6% of those with glioblastoma. A comparison of the data from the present series and from a similar Danish series of intracranial tumours in 533 children seen in the years 1935-1959 shows no significant differences in location or histology, a slight increase in annual incidence, and improved survival rates during the 50 years in question.

Adolescent↗

[Inflammatory pseudotumor--differential diagnosis in lung tumor in a child].

A case of a twelve-year-old girl with a big solid tumour in the right lung is presented. As malignancy could not be excluded, she was operated. A lobectomy was performed. Frozen section showed no malignancy. Histology showed inflammatory pseudotumour, which is a rare but important benign lung tumour in childhood. The recommended treatment is conservative resection.

Child↗

Immunohistochemical expression of IL-10 in mycosis fungoides.

Immunoreactivity of the cytokine IL-10 has been investigated in situ in mycosis fungoides (MF). Expression of IL-10 was detected using immunohistochemistry in skin biopsies (n = 8) and T-cell lines (n = 2) from mycosis fungoides patients. IL-10 positivity was seen in the dermal cell infiltrates and in T-cell lines in mycosis fungoides. The dermal IL-10 reaction in a skin biopsy from an active lesion in MF indicates the possibility for disease progression.

Adult↗

Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in psoriasis.

The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic factor towards monocytes, is produced by several cell types present in the skin. The in situ presence of MCAF/MCP-1 protein in the skin has, however, not yet been established. Using immunohistochemical techniques we have investigated the distribution of MCAF in skin from patients with different types of psoriasis and normal healthy volunteers. We report the novel finding that psoriasis has strong positive immunostaining for MCAF located to all the layers of the epidermis, except the stratum granulosum, in pustular, guttate and chronic plaque psoriasis. In the dermis, infiltrating cells in the perivascular aggregates and the blood vessels stained positive for MCAF. No significant differences were observed between the different subtypes of psoriasis except that strongly positive infiltrating cells were observed in the epidermal pustules in pustular psoriasis. In normals positive staining was observed in all the layers of the epidermis and in a few perivascular cells and blood vessels in the dermis. Where present in normal and diseased skin, eccrine ducts of sweat glands and sebaceous glands stained positive for MCAF. Arrector pili muscles were in all cases negative. These findings are consistent with a role for MCAF in attracting inflammatory cells, including monocytes, into the skin in psoriasis.

Chemokine CCL2↗

Antibodies to Pneumocystis carinii in Danish blood donors and AIDS patients with and without Pneumocystis carinii pneumonia.

Sera from 1) 8 AIDS patients with Pneumocystitis carinii pneumonia, 2) 13 HIV antibody-positive patients, 9 with AIDS and 4 with AIDS-related symptoms, all 13 without Pneumocystis carinii pneumonia, and 3) 36 healthy male blood donors, all HIV antibody negative, were examined for antibodies against Pneumocystis carinii using the indirect immunofluorescence antibody technique. Seven (87%) out of eight sera from group 1, 12 (92%) out of 13 sera from group 2, and 35 (97%) out of 36 sera from group 3 were positive. There was no significant difference between group 1 and 2, and group 2 and 3. The difference between group 1 and group 3 was significant (p = 0.03).

AIDS-Related Opportunistic Infections↗

Bacteriological autopsy. I. A methodological study.

The two aims of this investigation were: 1. To compare a swab culture technique with an imprint method in bacteriological autopsy. 2. To examine the influence of body manipulation on culture. Specimens were taken from the lungs and the spleen in 42 autopsies. For imprint a piece of sterile blotting paper was used. Point 1. Good qualitative agreement was found between the two methods. Print cultures enabled a quantitation at low numbers of bacteria. However, in most cases when growth was present the colonies were confluent, which did not allow counting. The lung cultures were 67%/69% positive (swab/print). For the spleen, the positive rate was 21%/42% (swab/print). In the cases representing the difference, only a few colonies grew on the print plates. Culture by means of a swab was found to give the same information as culture by imprint. Swabs are easier to handle but should be processed within a couple of hours. Point 2. In ten autopsies, cultures were taken with organs in situ after the organ block was removed and after an ordinary autopsy had been performed. A scoring system was used to compare the results. There was a clear correlation between positive cultures and manipulation of the organs. The specimens should be taken with the organs in situ.

Autopsy↗

Bacteriological autopsy. II. Comparison of a group of cancer patients with a control group.

A study of the results of bacteriological autopsy in a group of cancer patients compared with a control group was carried out. Autopsy was performed on 42 bodies within 24 hours of death. Thirty-two patients had died with a cancer and the remaining ten had died of cardiovascular disease. Tissue for microscopy and material and culture were taken from the same sites. The results of the inoculations were semiquantified, resulting in a culture score, and the results of the microscopy were classified according to presence of bacteria and kind of inflammation. Furthermore, grading was done according to the degree of inflammation and whether bacteria were seen at microscopy. The culture scores were significantly higher in the cancer group than in the control group. We found a significant correlation between score and presence of acute inflammation. Likewise, a significant correlation was found between score and presence of bacteria at microscopy. As a difference between the cancer group and the control group was seen, further research on bacteriological autopsy seems worthwhile.

Adult↗

Sarcomatous change in a previously benign osteofibroma in the maxillary sinus.

Ossifying fibromas of the jaws are generally well-defined benign tumors, so that adequate surgical treatment is usually associated with good therapeutic results. However, there are cases--especially in younger individuals with maxillary tumors--in which recurrences are seen, often with aggressive growth and subsequent local destruction. There is no characteristic histological appearance that identifies these "recurring types." A case is presented in which a benign ossifying fibroma was extirpated from a 17-year-old man. Twenty years later a recurrent tumor was found, in which histological examination showed development of a osteosarcoma. The clinical implications of this case are discussed.

Adolescent↗

Frequency of Alzheimer's disease in a postmortem study of psychiatric patients.

The brains from 100 consecutive patients dying in psychiatric departments were subjected to a neuropathological study with a quantitative evaluation of neurofibrillary tangles and senile plaques. Histologically, Alzheimer changes were found in 63.4% of the group with the clinical diagnosis of senile dementia and in 60% of the arteriosclerotic dementia group. In other clinical groups (schizophrenic, manic-depressive, and "other disorders") the percentage of Alzheimer changes was about 30. Thus, Alzheimer changes were not only present in the group of patients with the "correct" psychiatric diagnosis senile dementia, but were also frequent among patients with other psychiatric diseases where no clinical suspicion of Alzheimer's disease had been forecast. Alzheimer's disease may, thus, contribute to or be concealed by other psychiatric diseases and should be considered in all geronto-psychiatric cases.

Aged↗