Selection mechanisms as major determinants of survival after pulmonary metastasectomy.
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Biomedical subjects
Publications and source records attributed to T Aberg.
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UNLABELLED: The surveillance and monitoring of deviations from normality is an often used quality assurance weapon in private industry. In cardiac surgery, complications have often been monitored and reported, but mostly one at a time and in conjunction with a scientific study. METHODS: Using the clinic's data network including operating theatre, intensive care unit and ward, deviations from a normal postoperative course are registered by the patient's nurses. The deviations are registered by answering questions on all organ systems in front of a PC. Suitable definitions are available to the nurse. When the patient is discharged, the surgeon in charge will review the deviations noted and make a formal diagnosis on the patient's chart if appropriate. RESULTS: The data system has now been in use for 6 months. It was easily adopted by the nurses. The doctor's work is facilitated as relevant data are available to him when discharging the patient and making the discharge note. 58% of the patients have some kind of deviation from the norm, most commonly in the cardiovascular system (30% of the patients), respiratory system (22%), and surgically complicated postoperative course (17%). During the first months of registration it became apparent that too many patients had postoperative thrombophlebitis. By changing routines, the incidence of thrombophlebitis decreased from 5 to < 1%. CONCLUSION: Only about 40% of our patients go through a cardiac operation with a totally normal postoperative course. The registration system has turned out to be easily handled by our nurses and able to detect complications not immediately noticed in everyday clinical practice. A registry of this kind is highly dependent on its definitions and on the general 'norm' prevailing. Findings from such registries cannot therefore be immediately compared with those of other institutions. The research potentials of the registry as well as its role in quality assurance seem large.
OBJECTIVE: In a randomised study of 120 patients, undergoing primary operation for coronary heart decease, two groups were investigated as regards to the effects of heparin coated cardiopulmonary bypass on brain function parameters and general clinical outcome. The study group (n = 56) was perfused using an extra-corporeal circuit treated with covalent bonded heparin; the control group (n = 59) used an identical set-up without heparin treatment. Systemic heparin doses were calculated to achieve ACT levels of 250 and 500 s, respectively. Postoperative course was evaluated by examining a set of clinically relevant parameters including a detailed registry of postoperative deviations. Brain function was assessed by the biochemical marker S-100 and tests of memory performance. RESULTS: There were several signs of reduced operative trauma in the study group. Hospital stay was reduced by nearly 1 day (P < 0.05). Time on postoperative ventilatory support was approximately 4 h shorter (P = 0.009). Chest drain blood loss was decreased both at 8 (P = 0.01) and 24 h (P = 0.007) postoperatively. Body temperature was lower after surgery and especially on days 2 (P = 0.03) and 3 (P = 0.01). Perioperative creatinine elevation was significantly reduced (P = 0.03). Neurological deviations were fewer (P = 0.01). Brain function assessment revealed reduced plasma levels of S-100 both at termination of cardiopulmonary bypass (P = 0.008) and 7 h later (P = 0.04). However, no remediation of memory impairment could be demonstrated. CONCLUSIONS: Cardiopulmonary bypass with covalent bonded heparin attached to the extra-corporeal circuit in combination with a reduced systemic heparin dose seems to reduce safely and effectively the operative stress to the patient. There were also signs of improved cerebral protection.
OBJECTIVE: In order to ascertain the reasons why coronary revascularisation is performed, the appropriateness of these procedures and their outcomes, a national collaborative study encompassing 7 of 8 hospitals performing CABG in Sweden was undertaken. This article presents the indications and outcomes in the largest intervention group, chronic stable angina pectoris treated by first time CABG. METHODS: A prospective multi-centre study was carried out during a 3.5 month period in each centre. Patients (1039) with chronic stable angina pectoris undergoing first time CABG were enrolled. Patients' quality of life was recorded at the time they underwent angiography and again 6 months post-operatively. Mortality and serious peri-and post-operative complications were recorded. The study was designed and carried out by an independent government agency, the Swedish Council for Technology Assessment in Health Care (SBU) with a project group of representatives for the Swedish Societies for Cardiology, Thoracic Radiology and Thoracic Surgery. RESULTS: Median age was 66 years. A total of 80% were males. The mortality rates at 30 days and 6 months were 1.0 and 1.9%, respectively. A balloon pump was used for 0.9% of patients and 1.4% of them were on a respirator for more than 24 h. At recruitment, 43.9% of the patients reported having severe angina (CCS II/IV), 70.1% had angina > or = 3 times per week, and 53.1% used sublingual nitrates > or = 3 times per week. The corresponding results at 6 months were 6.7, 10.5 and 3.3%, respectively. Patient satisfaction with operative treatment was high. In comparison with the pre-operative status, quality of life was markedly improved after surgery. CONCLUSION: This study shows that CABG in chronic stable angina pectoris yields good outcomes with a low mortality and morbidity and a high degree of patient satisfaction and quality of life.
Analysis of prospectively registered incidents related to cardiopulmonary bypass (CPB) was initiated to establish the incident rate for 10 different oxygenator brands employed over a seven-year period in 5000 clinical perfusions. A general safety index (SI) was defined as the number of recorded incidents in a given series of oxygenators divided by its total number and multiplied by 100. Specific SI was calculated for each of the following categories: high-pressure drop, debris, gas exchange, leakage, material failure and oxygenator change-out. An SI of 0.2 was arbitrarily set as a reference and an acceptable safety level. An estimate of the relative risk for a particular oxygenator brand was compared with the reference by calculating the odd's ratio with a 95% confidence interval. The mean SI was determined to be 1.6, ranging from 0 for the Maxima CBAS and the Cobe CML to 2.92 for the Safe oxygenator. The dominating specific type of incident was HPD with an SI of 0.81 followed by debris, SI = 0.71. A systematic analysis of adverse events in CPB may be used to evaluate and to set standards, a method already employed in the pharmaceutical industry. Our results indicate that oxygenator safety margins may vary between different brands.
All vertebrate organs are formed from several cell types, and it is currently believed that interactions between the different components constitute the most important mechanism in the regulation of organ morphogenesis. In developing teeth morphogenetic interactions occur between the epithelium covering the facial processes and the underlying neural crest-derived mesenchyme. Morphogenesis is accompanied by differentiation of the various dental cell types, including the ameloblasts. Although ameloblasts differentiate terminally and start the deposition of enamel matrix only after the completion of crown morphogenesis, there is increasing evidence suggesting that the segregation of the ameloblast cell lineage may start much earlier. For example, the down-regulation of the North receptor, which in some other developmental system is associated with cell fate determination, is already seen in the dental epithelium prior to the bud stage. It is not known to what extent the differentiation of ameloblasts depends on tooth morphogenesis, and whether the same mesenchymal signals regulate morphogenesis and cell differentiation. There is evidence that growth factors act as morphogenetic signals. Bone morphogenetic proteins and fibroblast growth factors appear to regulate the initiation of tooth development, as well as the morphogenesis of the crown shape. However, the molecular nature of the signals regulating the advancing specialization of the cells in the ameloblast cell lineage remains unknown.
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Mammalian tooth forms are produced during development by folding of the enamel epithelium but the molecular mechanisms involved in the formation and patterning of tooth cusps are not understood. We now report that several key signaling molecules found in well-known vertebrate signaling tissues such as the node, the notochord, the apical ectodermal ridge, and the zone of polarizing activity in the limb bud are specifically expressed in cells of the enamel knot, which is a transient cluster of dental epithelial cells. By comparing three-dimensional reconstructions of serial sections following in situ hybridization we localized Sonic hedgehog, Bone morphogenetic proteins-2, -4 and -7, as well as Fibroblast growth factor-4 in nested domains within the enamel knot. We suggest that the enamel knot acts as a signaling or organizing center, which provides positional information for tooth morphogenesis and regulates the growth of tooth cusps.
Physical training affects carbohydrate metabolism and results in an increased insulin-stimulated glucose disposal. To investigate if carbohydrate and lipid metabolism would be affected by nutritional factors in optimally trained elite athletes, during a 1-year period we studies elite ice-hockey players on two Swedish top-performance teams. Players on one team were subjected to extensive dietary monitoring and intervention, whereas players on the second team continued their ordinary diet. Blood levels of insulin, C-peptide, glucose, hemoglobin A1C (HbA1c), lipids, and lipoproteins were measured repeatedly. Basal insulin levels and insulin resistance (IR) were significantly lower among athletes on both teams compared with a sedentary group, and muscle weight and body mass index were significantly higher. During the course of the study in the intervention group, insulin levels decreased (3.6 +/- 0.3 v 6.2 +/- 0.6 [mean +/- SEM], P <.05) in conjunction with a decreased relative fat energy content, but returned toward baseline levels when relative fat energy content increased. IR decreased in parallel (0.59 +/- 0.05 v l.12 +/- 0.12, P <.05) and followed a similar pattern, reverting toward baseline levels. Also, levels of HbA1c changed during dietary manipulation. No changes in these parameters were observed among the elite players from the team not participating in the diet regimen. In contrast to the parameters for glucose homeostasis, no significant changes were found in serum lipid or lipoprotein levels in either team during the course of the study. The results verify the presence of an improved carbohydrate metabolism in elite athletes. The observed changes in glycemic control and glucose homeostasis as a consequence of dietary modification demonstrate further that nutritional factors may affect carbohydrate metabolism also in well-trained athletes.
Apoptosis was localized in developing mouse teeth from initiation of morphogenesis to completion of cusp formation by using modified TUNEL method for serial sections and Nile Blue staining for whole mounts. Apoptosis was first detected at bud stage (E12-E13) in the central cells of the invaginating dental epithelium suggesting involvement of cell death in epithelial budding morphogenesis. During cusp development, apoptotic cells were located in the enamel knots, which are transient clusters of dental epithelial cells proposed to act as signaling centers directing the morphogenesis of tooth cusps. Apoptosis was also detected in other restricted epithelial cell populations including the dental lamina, ameloblasts, as well as stratum intermedium and stellate reticulum cells suggesting that the removal of these epithelial cells occurs by apoptosis. Apoptotic cells, presumably osteoclasts, were also located on the surfaces of the developing alveolar bone. When dissected E13 dental epithelium or mesenchyme were cultured in isolation, apoptotic cells were abundant throughout the tissues, whereas when cultured together, apoptosis was inhibited in both tissues close to their interface indicating that epithelial-mesenchymal tissue interactions prevent apoptosis. Epidermal growth factor (EGF) and fibroblast growth factor-4 (FGF-4) inhibited apoptosis in the dental mesenchyme when applied locally using agarose or heparin-coated acrylic beads, suggesting involvement of these or related growth factors in the prevention of apoptosis in dental tissues in vivo. The spatially and temporally restricted distribution patterns of apoptotic cells suggest multiple roles for programmed cell death in dental development. Of particular interest is the removal of the enamel knots by apoptosis which may terminate their tasks as regulators of the patterning of the tooth cusps. The apical ectodermal ridge (AER) of the limb bud has similar signaling characteristics as the enamel knot, and it also undergoes apoptosis. Hence, apoptosis may be a general mechanism for the silencing of embryonic signaling centers.
Signs of brain cell injury have been studied during the evolution of open heart surgery in the last quarter century. At the beginning of the period, it was possible to elucidate signs of brain injury with rather crude psychometric tests and clinical observations in seemingly normal patients having routine operations. Over the next 5 years, a marked improvement in psychometric scores was observed. However, a biochemical cerebral cell injury marker (adenylate kinase) showed increased levels in the cerebrospinal fluid, a finding indicative of brain cell injury. There was a correlation between cerebrospinal fluid levels of adenylate kinase and psychometric test results as well as between the marker levels and clinical signs. Because of the relative insensitivity of the psychometric tests used and the increasing difficulty in receiving permission for spinal fluid taps, other methods were sought. Refined psychometric memory tests were used and showed that even in the 1990s, there are subtle signs of brain cell injury during open heart operations. This finding was corroborated by using a highly brain-specific and brain-sensitive biochemical cell injury marker (S-100 beta) that increased during extracorporeal circulation and showed a correlation with clinical cerebral complications.
PURPOSE: The development of a thrombus extending into the veins is well recognized in renal cell carcinoma. We investigated the hypothesis that vein invasion alone has no adverse impact on survival but is a highly negative factor in other tumors. MATERIALS AND METHODS: In 200 consecutive patients invasion of the renal vein and vena cava was evaluated and compared with the clinical course. RESULTS: A total of 26 patients had vena caval and 47 had renal vein invasion. Patients with venous invasion had a significantly shorter survival but no survival difference was demonstrated based on the level of involvement. CONCLUSIONS: Our study indicates that vein invasion itself seems to be an important prognostic factor in renal cell carcinoma.
Classic studies on experimental embryology have shown that organ development in an embryo is largely regulated by so called inductive tissue interactions which mostly take place between epithelial and mesenchymal tissues. Also in the developing tooth, both morphogenesis and cell differentiation are governed by such interactions. Characteristic features of epithelial-mesenchymal interactions are that they are sequential and reciprocal, i.e. "induction" appears to consist of a chain of signaling events between the tissues. During the last decade, the expression patterns of numerous molecules have been studied in developing organs by in situ hybridization and immunohistology. Many of them have been associated with epithelial-mesenchymal interactions, and it is apparent that same molecules participate in regulation of morphogenesis in a number of different organs. Transcription factors such as Msx-1, Msx-2 and Egr-1, growth factors, including TGF beta's, BMPs, and FGFs, and structural proteins such as syndecan and tenascin are expressed in transient, time and space-specific patterns in many organ rudiments, including the tooth. We have shown by tissue recombination studies that the expression of certain molecules is indeed regulated by epithelial-mesenchymal interactions in the early tooth germ. In particular, during the early stages of morphogenesis, when the dental epithelium induces the condensation of mesenchymal cells around the epithelial bud, the expression of many genes is upregulated in the condensed mesenchyme. Previous experimental tissue recombination studies have indicated that at the same time the capacity to instruct tooth morphogenesis shifts from the dental epithelium to the dental mesenchyme.(ABSTRACT TRUNCATED AT 250 WORDS)
The existence of transient putative tooth anlagen in the prospective mouse upper diastema region has been documented previously in morphological studies. By in situ hybridization we investigated the expression patterns of the msx-1, msx-2, BMP-2 and BMP-4 genes, supposed to regulate early tooth development, in day 10-14 mouse embryonic upper diastema and molar regions, using 49 series of frontal sections. On the basis of comparison of the temporo-spatial expression patterns in both diastemal and molar tooth primordia we conclude that each of the four genes was expressed at least for some period simultaneously and at a comparable developmental stage in the transient and persisting dental primordia. BMP-2 and BMP-4 expression was downregulated in the diastemal dental primordia during their regression starting at day 13. The temporo-spatial pattern of BMPs expression may be associated with the disappearance of diastemal rudiments. Contrary to the molar anlage, we did not detect msx-2 gene expression in the diastemal dental rudiments after the stage of epithelial thickening. The deficiency of the msx-2 gene products may play a role in the growth retardation of diastemal dental primordia resulting in their subsequent involution.
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The lungs of pigs receiving long-term total parenteral nutrition (TPN) have been studied. A total of 20 pigs were tentatively infused with TPN through central venous catheters for 7 weeks. To secure adequate nutrition and gastrointestinal absorbance of nutrients, an additional full oral diet was given to eight of these animals. Fifteen control animals received Ringer solution through central venous catheters in addition to the oral diet. All animals infused with TPN for 7 weeks developed lung granulomas, a finding not observed in control animals. No lung granulomas were seen in three TPN animals sacrificed after 3 to 5 weeks owing to illness. All TPN animals also developed tissue reactions suggesting long-standing lung vascular inflammation. Similar vascular changes were seen in seven control animals that had bacterial infection or endotoxemia. The total amount of neutral fat in lung homogenate tended to increase in animals given TPN, and the linoleic acid content was significantly increased. In conclusion, long-term TPN caused lung granulomas in pigs. Vascular damage seemed to be accelerated by bacterial infection as well as by the TPN. The tissue reactions presumably involved long-term activation of monocytes/macrophages.
Standardized intra-abdominal hemorrhage was induced in 7 anesthetized pigs. The resulting hypovolemic shock was treated with pneumatic anti-shock garment (PASG) followed by intra-aortic balloon occlusion. The effects of this treatment on circulation, lung mechanics and gas exchange were studied. Hemorrhage was induced by pulling out sutures introduced in the inferior caval vein. We found that the use of PASG partially restored mean arterial blood pressure from 44 +/- 6 to 66 +/- 6 mm Hg. When intraaortic balloon occlusion was added, the arterial pressure returned to basal levels. Cardiac output fell severely due to the hemorrhage from 3.7 +/- 0.2 to 1.3 +/- 0.2 liters/min and could not be restored during the treatment. A severe fall in total lung compliance was recorded after inflation of the PASG from 18.6 +/- 0.9 to 10 +/- 0.7 ml/cm H2O, this was accompanied by a fall in alveolar ventilation. These findings emphasize the severe restriction in lung function that occurred during treatment with PASG. Both parameters returned to near normal values when the PASG was deflated and the intra-aortic balloon was inflated. Pulmonary vascular resistance increased by more than 400% and remained high during the study period. There was no change in arterial PO2, however the fall in mixed venous PO2 caused by hemorrhage was reversed at the end of the treatment. Indirect monitoring of cerebral function by continuous EEG showed a decreased voltage during the hemorrhage, this was reversed by the combined treatment. We conclude that the outlined treatment makes it possible to restore central hemodynamics and preserve cerebral function at least for a short period of time until definite surgical treatment can be performed. However, severe restriction on lung mechanics, especially when PASG was inflated, makes it probable that ventilatory support can be necessary in such cases.