Three-dimensional simulation of viscous-flow agglomerate sintering.

The viscous-flow sintering of different agglomerate particle morphologies is studied by three-dimensional computer simulations based on the concept of fractional volume of fluid. For a fundamental understanding of particle sintering characteristics, the neck growth kinetics in agglomerate chains and in doublets consisting of differently sized primary particles is investigated. Results show that different sintering contacts in agglomerates even during the first stages are not completely independent from each other, even though differences are small. The neck growth kinetics of differently sized primary particles is determined by the smaller one up to a size difference by a factor of approximately 2, whereas for larger size differences, the kinetics becomes faster. In particular, the agglomerate sintering kinetics is investigated for particle chains of different lengths and for different particle morphologies each having ten primary particles and nine initial sintering contacts. For agglomerate chains, the kinetics approximately can be normalized by using the radius of the fully coalesced sphere. In general, different agglomerate morphologies show equal kinetics during the first sintering stages, whereas during advanced stages, compact morphologies show significantly faster sintering progress than more open morphologies. Hence, the overall kinetics cannot be described by simply using constant morphology correction factors such as fractal dimension or mean coordination number which are used in common sintering models. However, for the first stages of viscous-flow agglomerate sintering, which are the most important for many particle processes, a sintering equation is presented. Although we use agglomerates consisting of spherical primary particles, our methodology can be applied to other aggregate geometries as well.

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

Soluble interleukin 2 receptors in patients after bone marrow transplantation.

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft-versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels.

Bronchiolitis obliterans organizing pneumonia and chronic graft-versus-host disease in a child after allogeneic bone marrow transplantation.

We report an 8-year-old boy who developed cough and respiratory failure 7 months after bone marrow transplantation (BMT) coinciding with the onset of chronic graft-versus-host disease (GVHD). Lung function data, imaging studies, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia. While this has been reported in association with chronic graft-versus-host disease in one adult case previously, we report the simultaneous occurrence of BOOP and chronic GVHD in a child after bone marrow transplantation for the first time.

Pulmonary capillary pressure and gas exchange after E. coli bacteremia in pigs.

In 9 Goettingen minipigs we studied the effect of E. coli bacteremia on effective pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance. Precapillary pressure gradient (dPa) was calculated as the difference between mean pulmonary artery pressure (MPP) and effective pulmonary capillary pressure (Pc) (dPa = MPP-Pc), postcapillary pressure gradient (dPv) as the difference between Pc and left atrial pressure (dPv = Pc-LAP). The disturbance of pulmonary gas exchange was quantified by the AaDO2 quotient 1-PaO2/PAO2. Live E. coli infusion resulted in hypodynamic circulatory failure. Cardiac index fell from 3.7 +/- 0.81 . min-1.m-2 to 2.2 +/- 0.71 .min-1.m-2 after bacteremia lasting for 3.5 h. Simultaneously venous pulmonary vascular resistance rose from 25% of total pulmonary vascular resistance before to 32% after 3.5 h bacteremia, thus raising Pc from 11 mmHg to 16 mmHg. The degree of respiratory insufficiency was correlated with changes of MPP, dPa and dPv: 1-PaO2/PAO2 = 0.2 + 0.035.dPv (r = 0.829). Our results show, that the longitudinal distribution of pulmonary vascular resistance changes during septicemia, thus raising Pc. This may be an important factor in the genesis of septic pulmonary failure.

[Phantom limb after amputation--overview and new knowledge]. / Phantom nach Amputation--Ubersicht, neue Erkenntnisse.

Almost all patients who have an extremity amputated will experience a phantom limb. Amputations of other parts of the body can also cause phantom sensations. One fourth of all women who undergo mastectomy relates phantom breast sensations. Phantoms are common following rectum amputation and may be significant as indicators of rectal tumor relapse. Visual phantoms can appear in patients who undergo eye amputation. Phantom phenomena occur after tooth extraction, ureterocystectomy, penectomy, plexus avulsion or spinal cord injury. The causes underlying phantom sensations are unknown. Sensory deprivation in animals causes reorganization of the cortical and subcortical maps: the areas representing the deprived input shrink and the neighbouring areas expand. The mapping allocates areas to represent the most used peripheral inputs. Every level of the nervous system seems to exhibit plasticity. The primary site seems to be the cortex. The cellular basis of plasticity is unclear. Significant sensory and motor reorganization was found in humans suffering phantom pain. There was a strong relationship between the amount of cortical reorganization and the intensity of phantom pain. These findings may influence the rehabilitation of the amputee. It was shown that pain and cortical reorganization can be reduced or even prevented by the active use of prostheses.

[Walter Matthias Diggelmann--the healing effect of story telling]. / Walter Matthias Diggelmann--Die heilende Wirkung des Geschichtenerzählens.

"Stories are weapons against disease" wrote Swiss writer WM Diggelmann (1927-1979). In writing stories he hoped to counteract the lethal course of his cancer. In the past it had helped him to overcome destitution and social disgrace and had given him identity. His last story Walking on the Island of St. Margaret is a ritual which conjures up an intact future by celebrating the past. Stories try to explain the world. They inform or clarify emotions. In telling stories, doctors and nurses demonstrate sympathy and understanding. Perhaps even greater benefits might be derived from patients telling their own stories. In doing so they emerge as individuals and give their lives purpose. Language is more than communication: it is shelter, link, home, ritual. Storytelling helps patients cope with their diseases. It is not clear whether this or any technique of psychotherapy has any effect upon the course of cancer.

Pulmonary artery occlusion-left atrial pressure gradient: an important factor in determining pulmonary venous vascular resistance in acute pulmonary failure.

OBJECTIVE: To determine whether pulmonary artery occlusion pressure (PAOP) accurately reflects left atrial pressure (LAP) in acute pulmonary failure. DESIGN: Sham-controlled laboratory investigation on Goettingen minipigs. INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live Escherichia coli bacteria in 11 animals; two animals served as the control group. Anesthesia was obtained with methohexital/piritramide and pancuronium bromide. MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by means of femoral artery, pulmonary artery, and left atrial catheters. Arterial-alveolar Po2 ratio was calculated to evaluate pulmonary function. Measurements were obtained before and after 1 and 2 hr of the E. coli infusion. Statistical significance was tested with analysis of variance. E. coli infusion caused the hypodynamic shock and respiratory failure. The PAOP-LAP gradient was -0.3 +/- 1.6 mm Hg before bacteremia and increased significantly (p less than .001) to 2.9 +/- 1.8 and 3.4 +/- 2.0 mm Hg after 1 and 2 hr of bacteremia, respectively. No significant changes occurred in the sham group. CONCLUSIONS: A PAOP-LAP gradient may develop during acute respiratory failure. Therefore, pulmonary venous vascular resistance may be underestimated if its determination is based on PAOP. An increase in bronchial to pulmonary blood flow and pulmonary venoconstriction are discussed as hypothetical causes of a PAOP-LAP gradient during acute respiratory failure.

Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia.

OBJECTIVE: To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. DESIGN: Prospective, controlled study with open-label assignment of animals to two groups. SETTING: Laboratory. SUBJECTS: Goehingen minipigs. INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. CONCLUSIONS: Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases.

Phase II study of doxifluridine in advanced squamous cell carcinoma of the head and neck.

We conducted a phase II trial with 5'-deoxy-5-fluoridine (doxifluridine) in advanced squamous cell carcinoma of the head and neck. The drug was given at the dose of 4 g/m2 daily X 5 every 3 weeks. Twenty eligible patients entered this trial, 12 being evaluable for response to doxifluridine. The majority of these patients received previous treatment for cancer. One complete and two partial remissions were observed (25%). Drug-induced toxicity consisted mainly of myelosuppression, mild nausea and vomiting, stomatitis and central nervous system side-effects. Other dosages or schedules for doxifluridine administration might be explored in poor-risk patients.

Diffuse pulmonary alveolar hemorrhage after allogeneic bone marrow transplantation.

Diffuse pulmonary alveolar hemorrhage (DAH) is a life-threatening complication following bone marrow transplantation (BMT). So far it has been seen preferentially after autologous BMT. Here, we describe a patient who presented with the picture of DAH after allogeneic BMT. We draw attention to the fact that the syndrome may occur after allogeneic BMT, too.

Perioperative myocardial infarction in coronary artery bypass surgery.

Perioperative myocardial infarction (PMI) as diagnosed by standard electrocardiograms (appearance of persistent Q-waves of at least 0.4 sec duration) and/or autopsy, occurred in 51 (3.8%) out of 1341 consecutive patients undergoing coronary artery bypass surgery using saphenous vein grafts. Retrospective analysis of the available data revealed that preoperative factors like sex, age, history of myocardial infarction, functional class, coronary risk factors, number of vessels diseased, and ventricular function had no influence on the incidence of PMI. However, intraoperative parameters, e.g., type and duration of cardiac arrest as well as technical errors leading to graft occlusion, significantly affected the incidence of PMI. The clinical relevance of PMI is indicated by a high early mortality of 25.5% as compared to 2.3% in patients without PMI. Improvement as well as complete alleviation of angina pectoris was less frequent in patients with PMI than in patients without PMI. The decrease in the rate of PMI from more than 18% in 1970 to less than 1% in 1978/79 confirms that such incidents should not be regarded as an inevitable risk but as a complication which can largely be avoided by proper operative technique.

Syndrome of the posterior and anterior root in a late isolated CNS relapse of c-ALL. Case report.

A 15 year-old girl who had c-ALL diagnosed in 1982 was presented in our clinic suffering from an ascended flaccid paresis and dysaesthesia of both legs. These are typical symptoms of polyradiculitis of the nerve roots L2-S2. A lumbal puncture revealed a pleocytosis with lymphoblasts which were up to 40% CD10 (cluster of differentiation) up to 70% CD19 and TdT (terminal transferase) positive. The diagnosis of late isolated CNS relapse was made. It is assumed that local residual infiltrations of leukemic cells into the nerve roots L2-S2 got into cell cycle and caused these rare CNS leukemia symptoms. Therefore the value of a craniospinal irradiation to prevent a CNS and systemic relapse is discussed.

[Hodgkin's disease in a Swiss family]. / Morbus Hodgkin in einer Schweizer Familie.

Hodgkin's disease was found in five members of the same generation in a large Swiss family. At presentation, the patients were between 20 and 30 years old. The histological diagnosis was confirmed in three patients. In one woman the differential diagnosis of histiocytic non-Hodgkin's lymphoma was considered. The patient history did not provide any conclusive evidence for environmental factors shared by all patients. Three siblings had grown up in the same household. They had never been in contact with the other pair of affected sisters. No clustering of cases in time occurred, as individual cases were diagnosed at least two years apart. Antibodies against Epstein-Barr viral capsid antigen were found in four patients (IgG: 1:10 to 1:160). There was no single HLA-haplotype common to all patients. However, two affected sisters were HLA-identical (paternal haplotype: Aw24(9), Bw62(15), DRw6; and maternal haplotype: A2, B7, DR2). Their brother with Hodgkin's disease was homozygous for A-, B- and DR-antigens. He shared all these antigens with his two affected sisters (A2, Bw62(15), DR2). A genetic predisposition in combination with environmental factors, in particular subclinical Epstein-Barr virus infection, may have been responsible for the development of Hodgkin's disease in this family.