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Biomedical subjects

E Andersen

Publications and source records attributed to E Andersen.

At least 19 recordsLinked to original sources

[Local resection of cancer of the Vater's papilla].

Tumours of the papilla of Vater are almost always adenocarcinomas and are often less than 2.5 cm in diameter. Lymph node metastases occur in one fourth of the patients with tumours with a diameter of less than 2.5 cm. Whipple's procedure has been the most common operation when attempting radical excision. Local resection has not won acclaim, even though the five year survival rates are often reported to be about the same as for Whipple's procedure. We present a patient who was operated on by local resection, and describe the operative technique.

Adenocarcinoma

[Abdominal wall hematoma].

We describe three case reports of hematomas in the abdominal wall muscles and discuss etiology, diagnostic findings and treatment. Abdominal wall hematomas are uncommon, and the condition is often misdiagnosed. One of our patients was laparotomised owing to suspected appendicitis, and one patient presented a tuberculous abscess that may have been an infected hematoma. Ultrasonographic examination or CT gives the correct diagnose. Conservative management is the treatment of choice unless bleeding is severe or the course is complicated by infection.

Abdominal Muscles

[Acute appendicitis. Preoperative observation time and diagnostic accuracy].

The indication for operative treatment of suspected acute appendicitis is based mainly on clinical examination. In this retrospective study of 327 emergency laparotomies the accuracy of the surgeons diagnosis was 69.4%. The overall rate of unnecessary laparotomy was 28.4%, and 45.6% of the operated females, aged 12 to 40 years, did not actually require surgery. The median postadmission delay before operation was three hours 28 minutes. With increasing observation time, the diagnostic accuracy was significantly decreased from 77.7 to 52.2%, and the incidence of perforation rose from 18.6 to 33.3%. 8.7% of the patients with a surgical condition suffered from excessive delay (greater than 12 hours) before surgery. There was no correlation between time of admission and operation and accuracy of diagnosis, but a considerable variation in accuracy between different surgeons. The difficulty in obtaining a correct pre-operative diagnosis in patients with suspected acute appendicitis is still a clinical problem of major concern.

Acute Disease

Anti-cyclosporine monoclonal antibodies and their anti-idiotopic counterpart: structure and biological activity.

In order to study the structural and functional mimicry of an antigen by anti-idiotypic antibodies, we generated anti-idiotopic monoclonal antibodies (anti-Id mAbs) against a mAb (R45-45-11) with specificity for the immunosuppressive cyclic undecapeptide cyclosporine (Cs; Sandimmune). Three out of five anti-Id mAbs inhibited the binding of Cs to the anti-Cs mAb R45-45-11. All anti-Id mAbs cross-reacted only with one (anti-Cs mAb V45-271-10) out of 19 anti-Cs mAbs. The anti-Cs mAb V45-271-10 recognizes an epitope on the Cs molecule which is very similar to that recognized by R45-45-11. R45-45-11 and V45-271-10 differ only by one amino acid in the variable region. The anti-Id mAbs which recognize combining site-associated idiotopes (Ids) reverse the blocking effect of the anti-Cs mAb R45-45-11 on Cs immunosuppression in vitro. The sequences of the variable regions of heavy and light chain of one anti-Id mAb were determined. X-ray analysis of the corresponding Fab fragment, either alone or complexed with the Fab fragment of the Id, is currently in progress.

Amino Acid Sequence

Molecular mechanisms of immunosuppression.

The immunosuppressive drug cyclosporin A (CsA, Sandimmun, SIM) is currently being evaluated in a variety of autoimmune disorders with some remarkable successes. Despite the wide empiric application of CsA, the precise mechanism of action of this drug remains elusive. To identify the molecular mode of action of CsA in the process of T cell activation, we have compared the biological profile of cyclophilin-binding cyclosporin analogues (CBCA), which lack immunosuppressive properties, with CsA. We have found that CsA binding to its intracellular receptor (cyclophilin) is required but not sufficient for immunosuppression. Moreover, inhibition of the peptidyl-prolyl cis-trans isomerase activity of cyclophilin does not seem to be relevant for the inhibitory effects of CsA. In analogy to the immunosuppressants FK506 and rapamycin, a specific structure at the 'effector' domain of the CsA molecule different from the immunophilin 'binding' domain determines the biological activity. Overall, a significant understanding of the structure-activity relationship of CsA has emerged. This will have a major impact on the identification of the precise mechanism of action of CsA and its side effects in the process of immunosuppression.

Amino Acid Isomerases

Rapid C-reactive protein (CRP) measurements in the diagnosis of acute appendicitis.

C-reactive protein (CRP) has been measured in plasma of patients with acute appendicitis and in controls without appendicitis to test the accuracy and diagnostic performance of a new rapid test kit for CRP (NycoCard CRP). The values obtained for CRP by the rapid test correlated well (Rs = 0.92) with the reference method for measuring CRP. The sensitivity, specificity and predictive values were calculated at different cut-off values. At values > 10 mg l-1 a sensitivity of 58% and a negative predictive value of 72% were found. Higher values of sensitivity were observed for men than for women, 69% and 44% respectively. Patients with acute appendicitis who had had symptoms for more than 24 h, had elevated CRP values (cut-off > 10 mg l-1) in more than 80% of cases. Our study shows that the rapid CRP test and the reference CRP test gave an almost identical result.

Acute Disease

Mouse erythrocyte rosette formation with malignant human B-lymphocytes re-evaluated: still a useful marker for differentiating mature B-cell malignancies.

We have re-evaluated mouse rosette formation (MRF) as a marker for B-CLL by estimating the fraction of mouse rosette forming B-lymphocytes (identified by CD20 monoclonal antibodies) in normal donors and malignant CD20+ cell proliferations (ALL, AML, B-NHL, B-HCL and B-CLL). Whereas this ratio was increased in B-CLL, all other CD20 positive malignancies showed mean ratios of less than 0.1. As part of a Danish multi-centre study, we furthermore prospectively analysed 86 patients and found that the mouse/CD20 ratio divided the 78 patients with monoclonal B-cell populations suspected of B-CLL in two distinct groups. In the low ratio group, three patients were categorized as leukaemized B-NHL and one as PLL. The remaining three patients with low ratio were clinically and immunologically (by SmIg density and CD5 expression) B-CLL patients suggesting a frequency of MR-negative B-CLLs of approximately 5%. In the high ratio group two of 70 patients were diagnosed as B-NHLs. Thirdly, MRF was a valuable parameter in patients, where transformation of disease is suspected, since it preceded clinical changes by several months. Thus, MRF is still a useful marker in the age of monoclonal antibodies.

Adult

Neutrophil elastase and its inhibitors in human gingival crevicular fluid during experimental gingivitis.

The relative concentrations and absolute amounts of neutrophil elastase and its two inhibitors, alpha 2-macroglobulin (alpha 2-M) and alpha 1-antitrypsin (alpha 1-AT), were determined in gingival crevicular fluid (GCF) collected from six dental students who refrained from brushing the upper left or right quadrant during three weeks. Plaque and gingival indices and flow of GCF were measured before, during, and after the three weeks of no brushing. Functional elastase, representing the enzyme complexed with alpha 2-M, was measured by use of a low-molecular-weight fluorogenic substrate. Elastolytic activity in GCF was also assayed by use of elastin as substrate. Antigenic elastase, representing the enzyme complexed with alpha 1-AT, as well as the inhibitors alpha 2-M and alpha 1-AT were measured by ELISA. After three weeks of plaque accumulation, the concentrations of both functional and antigenic elastase increased by a factor of about 3, whereas the concentrations of the inhibitors increased in a much higher proportion. No free elastase could be detected in GCF, as evidenced by the Sephadex G-75 elution profile of GCF, by the negative results obtained when elastin was used as substrate, and by the demonstration that pure enzyme kept its activity against the low-molecular-weight substrate after being saturated by alpha 2-M.

Adult

Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia.

Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia (CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23. There were 503 CD5+ and 37 CD5- cases. In the CD5+ cases, the cells typically expressed IgM, IgD, CD20, CD21, CD22, and CD23. In univariate analysis, age, clinical stage, IgM-fluorescence intensity, CD23, and FMC7 had significant prognostic importance, with high IgM-fluorescence intensity, high FMC7, and low CD23 expression being associated with a short survival. There was no significant difference in survival between 351 cases expressing IgMD and 55 cases expressing IgM without IgD, or between kappa and lambda light chain monoclonal cases. CD20, CD21, and CD22 had no prognostic importance. In Cox multiple regression analyses, age, CD23, IgM-fluorescence intensity, and clinical stage (International Workshop System) had independent prognostic importance. Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL. The survival of CD5- patients was on the borderline of being significantly shorter than that of CD5+ patients. The majority of the CD5- cases were FMC7+, CD23-, had strong IgM fluorescence, and had splenomegaly.

Aged

[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects].

A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.

Adult

[Therapy control of perphenazine. 2. Clinical aspects].

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

Adult

[Mirizzi syndrome].

Mirizzi syndrome is an uncommon cause of obstructive jaundice by impaction of stones in the cystic duct or in the neck of the gall bladder. The incidence is reported to be about one per cent of all patients undergoing cholecystectomy. A case of Mirizzi syndrome is presented, and the preoperative diagnostic approach and surgical treatment discussed.

Cholecystectomy

In vitro release of elastase from human blood and gingival crevicular neutrophils.

Peripheral PMNs were collected from blood, and crevicular PMNs separated by filtration from gingival washings in 13 patients, aged 22-75 y, who had varying degrees of gingivitis and periodontitis. After pre-incubation with cytochalasin B, the same number of crevicular and peripheral cells were incubated either in PBS (with Ca2+ and Mg2+) (spontaneous release) or in the same buffer containing increasing concentrations of FMLP (stimulated release); elastase activity was measured in the supernatant by a fluorometric technique. There was a higher spontaneous release of enzyme from crevicular than from peripheral neutrophils. The average elastase activity in the supernatant of 1 x 10(4) crevicular cells was more than five times higher than that obtained from the same number of peripheral cells. However, stimulated crevicular PMNs liberated smaller amounts of enzyme than did stimulated peripheral PMNs. These results suggest that crevicular PMNs are already releasing elastase, and are consistent with the possibility that lysosomal enzymes contribute to tissue damage during gingivitis and periodontitis.

Adult

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia.

Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.

Bone Marrow

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group.

In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage IE or IIE) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (greater than 50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age greater than 65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Adolescent

Femoro-popliteal artery occlusions treated by percutaneous transluminal angioplasty and enclosed thrombolysis: results in 55 patients.

Removal of fibrin from the site of a newly dilated femoro-popliteal occlusion may be an attractive way of preventing rethrombosis. A double balloon catheter with a dilating tip balloon and an occlusive balloon 10, 15 or 20 cm approximately were introduced percutaneously. Following successful dilatation of femoro-popliteal occlusions, the balloons were inflated on both sides of the lesion. The dilated segment was then isolated from the circulation. Through a sideport between the balloons 5 mg of tissue type plasminogen activator and 1000 IU of heparin were installed within the segment for 30 min. The authors report the results of 53 technically successful dilatations of femoro-popliteal occlusions followed by enclosed thrombolysis. A 100% patency at 3 months was noted in 33 patients having one to three run-off arteries, and the one year patency was 90%. In 20 patients, with no infrapopliteal run-off artery, four rethrombosis occurred within 24 h, and the one year patency was 62%. This difference is significant. (Log rank test, Chi-square = 4.73, p less than 0.05). We conclude that enclosed thrombolysis prevents early reocclusion following PTA of femoro-popliteal occlusions provided that at least one infra-popliteal artery is patent.

Aged