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Biomedical subjects

K Hagen

Publications and source records attributed to K Hagen.

At least 19 recordsLinked to original sources

Detection of c-erbB-2 activation in paraffin-embedded tissue by immunohistochemistry.

Commercially available monoclonal antibodies were tested for their ability to detect increased levels of c-erbB-2 protein in formalin-fixed, paraffin-embedded breast carcinomas. Of five antibodies studied, four (TAB-250, CB11, 3B5, and N3/D10) showed strong cytoplasmic membrane reactivity in 23% (11 of 47) of routinely processed tumors, although interpretation of the immunoreactivity with 3B5 and N3/D10 occasionally was difficult due to cytoplasmic granular staining. Since the c-erbB-2 oncogene is activated by DNA amplification and overexpression of mRNA and protein, the same tumors were analyzed for c-erbB-2 activation by other techniques. c-erbB-2 activation in these 11 tumors was confirmed by immunohistochemistry of frozen tissue (nine of nine tumors), in situ hybridization (nine of 11 tumors), and Southern blot analysis (five of eight tumors). In some of these tumors the failure to demonstrate c-erbB-2 DNA amplification may be due to the small percentage of malignant cells. One additional tumor showed probable c-erbB-2 protein overproduction based on strong immunoreactivity with two antibodies (TAB-250 and CB11), although no definite activation could be demonstrated by additional techniques. Three other tumors (6%) showed equivocal c-erbB-2 protein overproduction based on weak immunoreactivity only with TAB-250, although unequivocal activation could not be demonstrated by additional techniques. The 32 carcinomas (68%) that showed no significant immunoreactivity with any antibodies in routinely processed tissue also showed no detectable c-erbB-2 activation by additional techniques. We conclude that TAB-250 and CB11 are reliable antibodies for detecting c-erbB-2 protein overproduction in routinely processed tissue. TAB-250 also weakly stains a few tumors showing no definite c-erbB-2 activation by other techniques. Two additional antibodies (3B5 and N3/D10) detect c-erbB-2 protein overproduction in paraffin-embedded tissue, but are more difficult to interpret. A fifth antibody, TA-1, is an excellent reagent for use on frozen tissue, but prolonged formalin fixation may impair recognition of its antigenic epitope.

Adenocarcinoma

The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip fracture surgery. A placebo-controlled study.

A prospective, randomized, double-blind trial concerning thromboprophylaxis in 82 patients in whom hip fracture surgery was performed was conducted to compare a new low-molecular-weight heparin (Fragmin) with placebo. Deep venous thrombosis (DVT) was detected by 125-I-fibrinogen uptake test followed by ascending phlebography when positive. Sixty-eight patients completed the study, and a 50% reduction in the incidence of DVT was demonstrated: nine of 30 patients in the treatment group (30%) and 22 of 38 patients in the placebo group (58%) developed DVT. This significant difference was achieved by one daily dose of 5000 IU Fragmin subcutaneously, commenced preoperatively and continued for six days. There were no differences in bleeding or other complications in the two groups. Fragmin given once daily offers an effective and safe thromboprophylaxis in hip fracture surgery.

Aged

Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study.

In a double-blind, randomised study of thromboprophylaxis in patients undergoing total hip replacement, we compared a low-molecular-weight heparin with a placebo. Of the 120 patients enrolled, 112 completed the trial; 58 in the treatment group and 54 in the placebo group. Nine (16%) patients in the treatment group and 19 (35%) in the placebo group developed deep venous thrombosis, diagnosed by the 125I-fibrinogen uptake test (p < 0.02). Verification was obtained by phlebography in 86% of the patients. Prolonged surgery increased the risk of thrombosis in the placebo group but not in the treatment group (p < 0.05). There were significantly more cases of deep venous thrombosis in the placebo group during the first four postoperative days (p < 0.02). The groups did not differ with respect to peroperative and postoperative bleeding. Low-molecular-weight heparin offers safe and easily administered thromboprophylaxis in total hip replacement.

Adult

[Decompression of the carpal tunnel. Apropos of 16 reoperated cases].

The aim of surgery is the healing of disease, and also the preservation or even the reconstruction of the function of an anatomical structure. In 12 out of 16 second look operations after carpal tunnel release we found luxation or subluxation of the intracarpal content. This suggests that the instability created by surgical release of the retinaculum flexorum is an important factor in postoperative symptoms. Therefore we suggest replacing the lengthwise incision of the retinaculum flexorum by widening of this structure. This serves to enlarge the carpal tunnel without forfeiting the function of the retinaculum flexorum. It acts as a pulley, serves as an anchor to the thenar muscles, and allows mechanical protection to the underlying nerve. The satisfactory results obtained after secondary functional reconstructive surgery suggest the same principle should be applied at the first operation.

Adult

Aldicarb immunotoxicity: functional analysis of cell-mediated immunity and quantitation of lymphocyte subpopulations.

Adult female B6C3F1 mice received distilled water only or water containing 1.0, 10, or 100 ppb of aldicarb daily for 34 days. The target concentration of aldicarb present in the 100 ppb dosing solution was analytically verified. To further develop an immune profile of this compound, following aldicarb exposure, the ability of splenic natural killer cells and specifically sensitized cytotoxic T-lymphocytes to lyse YAC-1 lymphoma and P815 tumor cells, respectively, was evaluated. To supplement the functional assays, the impact of aldicarb exposure on the percentages and absolute numbers of total T-cells, T-suppressor, T-helper, and B-cells was evaluated. The absence of statistically significant effects on any of these parameters supports earlier reports that aldicarb does not result in adverse effects on the immune system of mice.

Aldicarb

Periodontal repair in dogs: effect of saliva contamination of the root surface.

This study evaluated whether periodontal repair following reconstructive surgery may be compromised by saliva contamination of the root surfaces during the surgical procedure. Circumferential periodontal defects, 5 to 6 mm in vertical dimension, were surgically created in the mandibular premolars in 9 beagle dogs and immediately treated. The denuded root surfaces in left and right jaw quadrants in 4 dogs were treated with either filter sterilized saliva or saline, while in the remaining 5 dogs the root surfaces were treated with unfiltered saliva or saline. The wounds were closed and allowed to heal for 4 weeks. The dogs were sacrificed and tissue blocks prepared for histometric analysis. Results showed no difference between teeth treated with filtered or unfiltered saliva and the saline treated controls. Connective tissue repair to the root surfaces exceeded 70% of the defect height in all experimental groups. Regeneration of cementum and alveolar bone was limited and did not exceed 30% of the defect height. The results indicate that contamination of the root surface by saliva during the surgical procedure does not necessarily compromise connective tissue repair to the root surface.

Alveolar Bone Loss

[Recurrent carpal tunnel syndrome. Problems and treatment].

Of 16 patients surgically treated for recurrent carpal tunnel syndrome, 60% demonstrated some degree of palmar subluxation or even luxation of the median nerve and flexor tendons intraoperatively, subsequent to previous simple division of the flexor retinaculum. During the past years, therefore, we have been performing a widening Z-plasty and reconstruction of the flexor retinaculum for surgical treatment of primary or recurrent carpal tunnel syndrome. In this paper, we present and discuss our operative technique and results.

Adult

Intramuscular lipoma of the lower limb. Long-term follow-up after local resection.

We report 12 patients with infiltrating muscular lipomas of the lower limbs all treated by wide resection. During follow-up averaging seven years, the tumour recurred in five patients. Our results and those reported by others suggest that, in order to avoid recurrence, this tumour, although benign, should be treated by total excision of the muscle or by compartmental resection. Hormonal imbalance was suspected in 9 of the patients but an oestrogen receptor analysis of the histological samples proved negative.

Adult

Correlation between concentrations of magnesium, zinc, and potassium in plasma, erythrocytes and muscles.

In 93 patients, consecutively subjected to laparotomy, we studied the correlation between concentrations of magnesium, zinc and potassium in plasma, erythrocytes and muscle tissue. Sixteen percent had hypomagnesemia, 27% hypozincemia, and 53% hypokalemia. There was no difference with regard to the concentration of magnesium and zinc in erythrocytes or in muscle tissue between patients with low and patients with normal/high plasma concentrations of these minerals. Potassium concentration per liter erythrocytes was slightly but significantly higher in patients with hypokalemia than in patients with normal plasma potassium. When expressed per mmol haemoglobin there was, however, no difference in erythrocyte potassium between these two groups. Neither did they differ with regard to potassium concentration in muscles. There was a highly significant correlation between the concentrations of magnesium, zinc and potassium in erythrocytes as well as in muscle tissue, and a significant correlation between magnesium and potassium in plasma. However, no correlation was found between the mineral concentrations in plasma, erythrocytes and muscles, neither for magnesium, nor for zinc or potassium. We therefore conclude that a valid test to estimate total body stores of these minerals cannot be based on analysis of erythrocytes.

Abdominal Muscles

Paget's disease of the anal margin.

A follow-up study of 22 patients with Paget's disease of the anal margin was conducted to determine the prevalence of invasive disease and coexisting visceral carcinomas, cure and survival rates. Seventy-three per cent of the patients suffered from persistent pruritus ani. Seven (32 per cent) patients had malignancy (invasive Paget's disease (n = 5) and coexisting visceral carcinoma (n = 2] and six (27 per cent) developed malignancy (invasive Paget's disease (n = 4) and coexisting visceral carcinoma (n = 2] during follow-up, giving an overall occurrence of malignancies of 59 per cent (95 per cent confidence limits: 36-79). The median follow-up period was 9 (range 0.5-25) years. No difference in length of history could be found between patients with or without malignancy. The estimated cure rate by actuarial analysis among radically treated patients was 64 per cent (95 per cent confidence limits: 43-91) at 1 year and 45 per cent (95 per cent confidence limits: 18-72) at 8 years after primary treatment. The 5- and 10-year crude survival rates of 54 per cent and 45 per cent, respectively, were significantly lower than the corresponding values of 84 per cent and 60 per cent for the normal population (P less than 0.01). Patients with persistent pruritus ani and a perianal skin lesion should be biopsied frequently. If Paget's disease is diagnosed, physical examination of the patient and anorectal region must be done carefully and repeatedly.

Aged

Adenocarcinoma of the anal ducts. A series of 21 cases.

The records of 21 patients treated for adenocarcinoma of the anal ducts between 1943 and 1982 were reviewed. The patients were followed until death or current status in April 1987. The median follow-up period was eight months (range, 3 to 144 months). Fifteen patients had an erroneous diagnosis made at first physician visit resulting in a median doctor's delay of 14 months (range, 3 to 24 months) before correct treatment was carried out. Nine of the tumors were localized perianally (ischiorectal space), seven anally, and five in a fistula-in-ano. Tumors localized anally were significantly smaller and had a significantly shorter history than perianally or fistula-in-ano localized tumors (P less than .05 for each localization). Three patients with anal tumors had their diagnosis made accidentally by routine histologic examination of an excised hemorrhoid. First examination revealed distant metastases in 13 patients and follow-up examination revealed regional or distant metastases in seven patients. Modes of treatment were wide local excision (N = 3), abdominoperineal resection (N = 3), colostomy (N = 9), and radiotherapy (N = 2). Twenty of the 21 patients died within 18 months due to the cancer. One long-term survivor was observed; the patient was alive 12 years after local excision of the tumor without evidence of recurrent disease. The crude five- and 10-year survival was only 4.8 percent.

Adenocarcinoma

Long-term prognosis after radical treatment for squamous-cell carcinoma of the anal canal and anal margin.

Sixty-seven of 100 (67 percent) and 24 of 58 (41 percent) apparently radically treated patients with squamous-cell carcinoma of the anal canal (AC) and the anal margin (AM) developed recurrent disease during a median observation time of ten years (range, 0 to 38 years). A significantly higher number of patients treated for AC tumors with local excision had recurrent disease compared with patients treated with abdominoperineal resection (P less than .05). Twenty patients with AC tumors had local recurrence, 21 regional recurrence, and 26 visceral metastases. Eighteen patients with AM tumors had local recurrence, five regional, and one brain metastases. The latest recurrences among AC and AM tumor patients were diagnosed 11 and nine years after primary treatment, respectively. The estimated cure rate by the actuarial method after 15 years was 26 percent and 53 percent for AC and AM tumors, respectively. Thus, if recurrent carcinomas of the anus are to be detected early, frequent life-long control examinations are necessary. It is obvious from this study that, in order to reduce recurrent disease of carcinoma of the anus, new treatment regimens must be tried under controlled circumstances. Surgical therapies alone are clearly insufficient in the treatment of carcinoma of the anus.

Actuarial Analysis

Does an erroneous diagnosis of squamous-cell carcinoma of the anal canal and anal margin at first physician visit influence prognosis?

Patients with squamous-cell carcinoma of the anal canal (n = 125) and its margin (n = 76) were divided into five groups: those with an erroneous diagnosis and a correct diagnosis made at first physician visit; those with a history of less than six months, between six and 18 months, and more than 18 months. Patients with canal tumors had an erroneous diagnosis made more frequently than patients with margin tumors. In both groups patients with an erroneous diagnosis had longer histories than patients with a correct diagnosis. Among patients with erroneously diagnosed canal tumor, pain, the feeling of a lump, anal discharge, and pruritus ani occurred less frequently than among correctly diagnosed patients. The prognosis was worse among patients with erroneously diagnosed canal tumors compared with correctly diagnosed patients. Such a difference could not be found among patients with margin tumors. There was a gradual worsening of the prognosis among patients with increasing length of history and canal tumors, in contrast to patients with margin tumors, in whom only a history of more than 18 months was associated with a worse prognosis.

Adult

Hepatoblastoma: an immunohistochemical and ultrastructural study.

The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm.

Carcinoembryonic Antigen

Immunity to murine leukemia induced in susceptible mice by transfected mouse fibroblasts.

A cultured cell line of mouse fibroblasts was transfected with DNA from murine leukemia cells expressing a previously characterized tumor-associated antigen. Antigen-positive cells were used as immunogens in an immunotherapy protocol to determine if they stimulated resistance to the malignant proliferation of the leukemia in susceptible mice. For the experiments, LM(TK-) mouse fibroblasts, a thymidine kinase-deficient mouse cell line, were cotransfected with DNA from ASL-1 murine leukemia cells and the plasmid pSV2neo conferring resistance to Geneticin. Integration of the plasmid into cellular DNA was confirmed by restriction digest blot analysis. A/J mice, highly susceptible to the malignant proliferation of passively transferred ASL-1 leukemia cells, were immunized with the transfected cells. Animals receiving two prior injections of antigen-positive transfected cells and then challenged with an injection of viable ASL-1 cells survived longer than animals in the unprotected control group or in the group receiving immunizations with LM(TK-) cells transfected with plasmid only (p less than 0.01). Some of the mice appeared to have rejected the tumor and lived more than 80 days. One group of protected animals rechallenged with a second injection of ASL-1 cells, 40 days after the first, survived for more than 50 additional days, without evidence of recurrent disease.

Animals

Formation of macrophage (M) colony-stimulating factor by murine leukemia x fibroblast hybrid cells.

Clonogenic assays for M, GM, and G precursors of rat or mouse marrow cells were performed in the presence of medium conditioned by the growth of ASL-1 leukemia X LM fibroblast hybrid cells. Both GM- and M-colony-forming units (CFUs) were present in marrow cultures maintained in conditioned medium (CM) from hybrid cells (up to 162 +/- 10 total colonies per 10(5) cells) and from LM cells (65 +/- 5). Conditioned medium from ASL-1 cells did not lead to the formation of CFUs. The hybrid cell-derived CM supported the development of M and GM-CFUs from the marrows of DBA, CAF1, BDF1, C3D2F1, and C57B1/6 mice as well as Lewis, Brown Norway, and Wistar Furth rats. G-CFU were not detected in any of the preparations. Hybrid cell-CM supported the long-term growth and proliferation of macrophage-like cells from mouse spleen, consistent with the presence of M-colony-stimulating factor (CSF). Evidence that M-CSF formed by the hybrid cells and M-CSF formed by L cells shared structural features was provided by antibody neutralization studies. The CFU-promoting activity of hybrid cell-derived M-CSF was neutralized by an antiserum raised in goats against M-CSF purified from L cells. Independently prepared ASL-1 X LM hybrid cells, like the original, led to the formation of GM and M-CFUs. Attempts to detect each of several other previously defined growth factors in medium conditioned by the hybrid cells were unsuccessful. Interleukins 1, 2, and 3; B cell growth factors interferons alpha, beta, and gamma; erythropoietin; and burst promoting factor were not detected.

Animals