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Biomedical subjects

J L Nielsen

Publications and source records attributed to J L Nielsen.

At least 19 recordsLinked to original sources

Penetrating intrapericardial wounds: clinical experience with a surgical protocol.

BACKGROUND: From 1972 to 1977, a treatment protocol was developed at our institution for patients with suspected penetrating intrapericardial wounds. It consists of immediate transport to the operating room, pericardial decompression by subxiphoid pericardial window under local or light general anesthesia in patients in stable condition, and median sternotomy and operative repair with limited use of cardiopulmonary bypass. METHODS: The records of 79 consecutive patients with acute penetrating intrapericardial injury who underwent operation from March 1978 to July 1991 were reviewed. There were 59 patients (75%) with stab wounds and 20 (25%) with gunshot wounds. Wound location was as follows: right ventricle, 33 (42%); left ventricle, 28 (35%); multiple sites, 8 (10%); atrium, 5 (6%); and great vessels, 5 (6%). RESULTS: Subxiphoid pericardial window was performed under local or light general anesthesia in 53 patients (67%). Cardiopulmonary bypass was required in only 4 patients. Overall mortality was 6%. CONCLUSION: Approach to a trauma victim must be systematic. We believe one treatment protocol for patients with suspected penetrating intrapericardial wounds is effective.

Adolescent

[Kasabach-Merritt syndrome].

Kasabach Merritt syndrome, first recognized in 1940, is characterized by haemangiomatosis, thrombocytopenia and intravascular coagulation. It is most often seen in children, rarely in adults. The mortality rate is 20-30%. Treatment is by removing the haemangiomatosis and correcting the consumptive coagulopathy. The purpose of this paper is to present a patient with Kasabach Merritt syndrome with haemangiomatosis in the spleen and the liver. A review of the relevant literature is given.

Adult

Connective tissue components in serum in multiple myeloma: analyses of propeptides of type I and type III procollagens, type I collagen telopeptide, and hyaluronan.

The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C-terminal propeptide of type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N-terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex- and age-matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 micrograms/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 micrograms/L; P < 0.01) and hyaluronan (median 122 vs. 45 micrograms/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum beta 2-microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen-derived peptides or beta 2-microglobulin. The MM group was followed for 9-25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown.

Aged

Studies of serum protein complexes with nickel using crossed immunoelectrophoresis.

Crossed immunoelectrophoresis of human serum spiked with nickel in the range 0.85-24 mmol Ni/L was used to study nickel-protein complexes. These high concentrations, which are far higher than the physiological level (approximately 7.8 nmol/L), were used to saturate both high and low affinity binding sites. Addition of increasing amounts of nickel resulted in dose-dependent changes of the electrophoretic patterns of prealbumin, alpha-1-lipoprotein, alpha-1-antitrypsin and alpha-2-macroglobulin. Radioactive 63Ni was used for crossed immunoelectrophoresis autoradiography experiments for further identification of nickel-protein complexes. When a 63Ni pulse of 740 kBq/application was used, many human serum proteins were labeled. When using a 63Ni pulse of 185 kBq/application only albumin and alpha-1-antitrypsin were visualized clearly. The binding of large amounts of nickel to albumin, visualized by autoradiography, may reflect the high abundance of albumin in human serum as compared to other serum proteins. Addition of nickel to serum proteins resulted in liquid phase precipitation of serum proteins, and rocket immunoelectrophoresis was used to demonstrate that IgG in particular is precipitated. This precipitation of serum proteins may disturb the elution profile when chromatographic techniques are used to analyze nickel-protein complexes. Consequently, immunoelectrophoretic methods may also be attractive alternatives to column chromatographic techniques. The present study demonstrated that, besides the nickel-binding of albumin and alpha-2-macroglobulin, several other serum proteins have nickel-binding affinity.

Blood Proteins

Assessment of injury in transplanted and nontransplanted lungs after 6 h of cold storage with glutathione.

Single-lung transplantation after 3 h of hypothermic storage produces bilateral lung injury [pulmonary reimplantation response (PRR)]. We hypothesized that glutathione (GSH) hypothermic storage would protect both lungs from PRR for extended preservation times and that differences in injury and protection would be realized between the graft and the nontransplanted lung. Mongrel dogs underwent left single-lung autotransplantation after preservation for 5-6 h in Euro-Collins (EC) solution, EC plus exogenous GSH (EC+GSH), or Viaspan (VIA) at 4 degrees C. Lung injury was measured in both lungs after 1 h of reperfusion. EC dogs demonstrated significant increases in lung edema, lipid peroxidation, and alveolar neutrophil recruitment in the lung graft and to a less extent in the nontransplanted right lung compared with control dogs (P < 0.05). Edema, lipid peroxidation, and alveolar neutrophils were significantly reduced in both lungs from EC+GSH and VIA dogs compared with lungs from EC dogs (P < 0.05). An increase in large-pore permeability was measured in the lung graft from EC dogs compared with all other lungs. Bronchoalveolar lavage fluid lactate dehydrogenase and total protein concentrations were elevated in both lungs from all three groups of tranplanted dogs compared with those of control dogs (P < 0.05). These data suggest that GSH-containing solutions attenuate the PRR after 6 h of ischemic hypothermic storage but that the protection is incomplete. Mechanisms of injury affecting the lung graft during the PRR appear to differ from those affecting the nontransplanted lung.

Animals

Pneumococcal septicaemia and meningitis in vaccinated splenectomized adult patients.

A retrospective survey of the occurrence of pneumococcal septicaemia and meningitis in splenectomized adults was performed at a regional haematological centre after the introduction of pneumococcal vaccination in 1978. During this period 4 episodes of pneumococcal septicaemia were observed in 3 vaccinated, splenectomized patients. In all episodes the pathogenic strain was of an unusual serotype not included in the vaccine lending indirect evidence for the clinical efficacy of the pneumococcal vaccine, even in immunocompromised patients.

Adult

[Non-Hodgkin lymphoma in the elderly].

Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Danish population-based NHL-register. Of these, 602 (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the population defined as "elderly" patients in the present study. Their average annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and extranodal manifestations were more frequent among elderly patients. The most common sites of extranodal involvement were stomach (21% of all extranodal cases) and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p < 0.01) in elderly patients as compared to their younger counterparts (< 70 years), who on the other hand had a lower occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival for the elderly patient population was 35% (median: 1.7 years), and for patients aged < 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor prognostic factors for elderly patients were identified by multivariate analysis: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and 1.6.

Age Factors

Double minutes are frequently found in ovarian carcinomas.

Double minutes (dmins) are acentric chromosomal-like entities that are important in the etiology of cancer because they are known to harbor amplified oncogenes and drug resistance genes. Because dmins can be unequally partitioned at mitosis they have the ability to confer genetic diversification rapidly. Selective pressures operative in vitro may be quite different than those in vivo; therefore, tumor cells which harbor dmins could be selected against during short-term in vitro propagation. We wanted to determine the incidence of dmins in human ovarian cancer cells obtained from fresh ovarian specimens with an absolute minimum of culture time (6-24 hours). In "direct" chromosomal preparations obtained from these clinical specimens we found dmins present in 88% of these samples. This remarkable finding that dmins are found so frequently in ovarian cancers underscores the importance of gene amplification in human tumor biology. Therefore, the presence of dmins in patient specimens indicates that these unstable genetic elements may play a significant role in the maintenance or progression of malignancy.

Ascites

Ph-positive chronic myeloid leukemia with loss of the segment distal to M-bcr.

We describe a patient with chronic myeloid leukemia (CML) and a 22q- but no 9q+ chromosome. Southern blot analysis showed a BCR rearrangement. The patient soon developed profound and superficial thrombophlebitis in arms and legs and died from pulmonary embolisation 15 days after diagnosis. Five CML cases with a deletion of 22q but no known translocation of 22q11----qter have been described earlier. The present patient is the first such case, however, in whom a BCR rearrangement has been demonstrated.

Blast Crisis

Risk of major elective operation after myocardial revascularization.

Although an increased surgical risk of ischemic myocardial disease is widely accepted, amelioration of this risk after coronary artery bypass is poorly defined. We compared the outcomes of major elective general and peripheral vascular operations in 181 patients with prior coronary artery bypass grafting (CABG) with outcomes in an age-, gender-, and procedure-matched group without prior CABG (NOCABG). Despite the perception of a greater operative risk in the CABG patients (more CABG patients in American Society of Anesthesiologists [ASA] class III and fewer in ASA class I, p < 0.001), mortality (1.1% CABG versus 2.8% NOCABG) and morbidity (18.8% CABG versus 18.5% NOCABG) rates in the two groups were not significantly different. For patients who have undergone successful CABG, it appears that: (1) the risk of subsequent elective major general and vascular surgical operations is similar to that of an age-, gender-, and procedure-matched cohort, and (2) the mortality rate after elective operations is low.

Age Factors

Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group.

Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.

Aged

Initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of interferon-alfa-2b therapy in chronic myelogenous leukemia.

Eleven previously untreated patients with chronic-phase Philadelphia-chromosome-positive chronic myelogenous leukemia were treated with cytotoxic chemotherapy followed by interferon-alfa-2b (IFN-alpha) maintenance. Initial chemotherapy consisted of three cycles of mitoxantrone 10 mg/m2 on day 1 and 2, and cytarabine 100 mg/m2 daily for 5 d. Complete hematological response was obtained in 9 (82%) patients with moderately associated toxicity. However, cytogenetic responses after three cycles were poor and transient (1 partial suppression and 2 minor suppression of Ph chromosome). Maintenance therapy with IFN-alpha was started in 10 patients at 5 x 10(6) U/m2 daily with dose reduction if hematologic toxicity or severe side-effects occurred. Of 9 evaluable patients treated for more than 3 months, 6 patients maintained a complete hematological response, whereas 1 patient remained in partial remission and 2 patients showed progressive disease. Cytogenetic evaluation showed partial suppression of Ph chromosome in 1 patient, whereas 1 patient had a minor response and 5 patients had no change or evolution of new chromosome abnormalities. As the results are not superior to IFN-alpha treatment alone, it is concluded that initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of therapy in CML.

Adult

[Malignant hematologic diseases. Diagnosis and treatment. A clearing report].

The malignant haematological disorders comprise the main groups leukemia, malignant lymphoma and multiple myeloma and the potentially malignant disorders: myelodysplastic syndrome, polycythaemia vera, myelofibrosis and M-component of uncertain significance. The common feature of all these disorders is monoclonality, i.e. they originate from one single cell. Around 2,000 new cases are diagnosed per year in Denmark. Because of the relative small number of patients, complex diagnosis and treatment (especially the possibility of cure on intensive treatment) a high degree of centralization is warranted to secure an evenly distributed high level of patient care and research. The present rules for referral of patients are unsatisfactory. A new referral system is proposed based on a common set of rules, agreed upon by five haematological centers in Denmark and the surrounding region, comprising diagnostic procedures, treatment, research and development for all haematological patients in the area. Based on these common rules (functional centralization) it is decided whether the individual patient can be treated in the primary hospital or should be referred to a center (geographical centralization). Recommendations about diagnosis, treatment and referral are made in this report. Detailed suggestions are given for diseases which may be treated locally whereas no detailed regimens are given for diseases and disease stages which should be centralized. In the latter cases, the main emphasis is placed on a presentation of treatment results.

Denmark

Antibody persistence in splenectomized adults after pneumococcal vaccination.

16 splenectomized adults, all vaccinated with a 14-valent pneumococcal vaccine (Pneumovax) 1978-79 had their pneumococcal antibody concentrations measured before and up to 10 years after vaccination. The antibody concentrations after vaccination declined to 71% in 2 years and remained at this level during the 10-year study period. Further studies are needed to see whether this applies to all vaccinated splenectomized adults.

Antibodies, Bacterial

Reversal of flunitrazepam sedation with flumazenil. A randomized clinical trial.

Fifty-nine male patients scheduled for transurethral resection of the prostate under flunitrazepam sedation and spinal analgesia were randomized in a double-blind trial to reversal of sedation with either the benzodiazepine antagonist flumazenil or placebo. Judged by degree of sedation, comprehension and cooperation as well as by estimation of orientation in time and space, flumazenil was superior to placebo (P less than 0.001). The median duration of anterograde amnesia was 16 min after flumazenil and 75 min after placebo (P less than 0.001). Adverse events were more frequent with placebo (P greater than 0.05), while no differences were evident with regard to laboratory data or cardiorespiratory function.

Aged