A prospective randomised control study: reduction of children's pain expectation using a picture book during blood withdrawal.

OBJECTIVES: Blood drawings are very painful and stressful for children. In a prospective control group study we investigated if using a picture book could reduce the children's pain expectation. In addition, the children's pain experience and the observed pain behaviour was monitored. PATIENTS/METHODS: Block-randomization were used and 120 children at the age of 6-12 years who were visiting the general pediatric and coagulation outpatient clinics were included in this study. Pain expectation and experience were assessed with the Face-Pain-Scale-Revised and the pain behavior with the Faces-Legs-Activity-Cry-Consolability Scale. Multivariate covariance analysis was used for data analysis. RESULTS: The results showed that with statistical controlling the influence of the primary pain expectation (baseline) the pain expectation before blood withdrawal was reduced significantly (p=0.001) and effectively (ES=0.56) using the picture book. Children who received no local anaesthesia reported that they felt less pain during blood drawing after reading the picture book. The few children with local anaesthesia reported no benefit from the picture book. The observed use of local anaesthesia was very heterogeneous. CONCLUSIONS: The results recommend the usage of this picture book in everyday practice, if the use of local anaesthesia could not be used in an appropriate way.

Homozygous point mutations in platelet glycoprotein ITGA2B gene as cause of Glanzmann thrombasthenia in 2 families.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by quantitative and/or qualitative defects of the platelet glycoprotein (GP) IIb/IIIa complex. Physiologically, the integrin GPIIb/IIIa binds Von Willebrand factor and fibrinogen on activated platelets. GT is caused by genetic alterations in ITGA2B or ITGB3 (genes encoding GPIIb and GPIIIa).This study describes 2 siblings diagnosed with GT type I associated with homozygous point mutations in ITGA2B. All patients presented with typical bleeding disorder including moderate hematomas, petechiae, and mucocutaneous bleedings.Both siblings showed severely reduced platelet aggregation especially after stimulation with collagen and adenosine diphosphate. Absence of platelet GPIIb/GPIIIa complex was determined using flow cytometry. Molecular genetic analysis revealed 2 distinct homozygous point mutations in exon 18 of ITGA2B. Family 1 was identified with c.1878G>C and family 2 with c.1787T>C substitution. While the c.1787T>C mutation causes a single amino acid substitution p.I565T, the c.1878G>C mutation (p.Q595H) is predicted to induce a mRNA splicing anomaly.These mutations were identified as cause of GT type I in the described patients. Patients with GT should be documented in a prospective register to verify the correlation between the severity of bleeding symptoms and the pathogenic mutation. This can have effects on therapeutic decisions.

Empyema thoracis: lack of awareness results in a prolonged clinical course.

OBJECTIVE: To assess the hypothesis that empyema thoracis (ET) is a problem often not optimally treated. Long delays in diagnosis are common, long hospital stays are typical and recovery with surgery is relatively rapid. DESIGN: A chart review. SETTING: The Regina Health District associated hospitals, a tertiary referral centre. PATIENTS: The charts of 34 consecutive patients having primary respiratory tract disease and seen during the 6-year period Apr. 1, 1991, to Mar. 31, 1997, were identified. OUTCOME MEASURES: Patient presentation, time until diagnosis of ET, number of radiologic investigations, microbiologic features, treatment methods, postoperative course and mortality. RESULTS: The mean delay in diagnosis, defined as the time of admission to the time of correct diagnosis, was 44.2 days (range from 0 to 573 days) and the mean delay until thoracic surgery referral was 47.4 days (range from 0 to 578 days). On average each patient underwent CT 10.1 times, had 2.6 percutaneous drainage procedures and 2.0 chest tube insertions. The mean time from the first percutaneous chest drainage to the date of diagnosis was 29.8 days (range from 0 to 564 days). Of the 26 patients who underwent CT, the mean time from the first CT of the chest to the date of diagnosis was 9.5 days (range from 0 to 75 days). Cultures of pleural fluid grew no organisms in 17 patients; in the remaining 17 patients cultures grew 23 different microorganisms. Of 26 patients who were referred for surgical opinion, 18 underwent decortication; 8 were not considered to be surgical candidates. Pathological examination showed 17 cases of inflammatory empyema and 1 case of mesothelioma (unrecognized clinically). The mean length of hospital stay postoperatively was 15.2 days. CONCLUSIONS: Early suspicion of ET facilitates its treatment, resulting in fewer investigations and shorter hospital stays. When percutaneous drainage does not eliminate pleural effusions, empyema must be considered. Recovery from surgical decortication is rapid in comparison with the typical protracted preoperative hospital course.

Aortic wall tension as a predictive factor for abdominal aortic aneurysm rupture: improving the selection of patients for abdominal aortic aneurysm repair.

Aortic wall tension was determined in 40 patients to assess its predictive value in abdominal aortic aneurysm (AAA) rupture. A 3-year retrospective analysis of 243 patients with ruptured AAAs and 45 patients with intact AAAs was conducted. The 288 patient sample was limited to the 40 patients with an abdominal CT scan investigation. Aortic wall tension was calculated using blood pressure data and measurements from computerized tomographic (CT) images of 26 patients with intact AAAs and 14 patients with ruptured AAAs in accordance with LaPlace's Law for wall tension: P x R/W, where P = mean arterial pressure (MAP), R = radius of the vessel, and W = wall thickness of the vessel. The wall tension was approximated with the more readily accessible patient parameters of AAA diameter, MAP, height, and weight. This approximation was termed the body mass index (BMI)-pressure approximation for tension (BPAT), which is AAA diameter/BMI x MAP. Data were analyzed using one-sided t-tests, chi-squared tests, and a regression analysis for the relationship between aortic wall tension and the BPAT. AAA wall tension is a significant predictor of pending rupture. BPAT used to approximate the actual tension in the AAA wall is a more sensitive predictor of rupture than aneurysm diameter alone. A prospective study has been initiated to validate these conclusions.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

Exercise prescription for patients with pacemakers.

When developing an exercise program for pacemaker patients, basic information about the pacemaker must be understood. Atrial, ventricular, and dual-chamber devices can produce varying exercise responses and impact the exercise prescription. The type of rate adaptive sensor the pacemaker has will affect the nature of heart rate response, and therefore, must be taken into account when prescribing exercise. While rate modulation is used with most chronotropically incompetent patients, individuals with VVI pacemakers will also benefit from regular exercise. Although the value of exercise testing pacemaker-dependent patients for ECG interpretation may be limited, it is useful in determining exercise capacity and ensuring proper pacemaker function. Participation in a supervised exercise training program can greatly enhance the follow-up and management of pacemaker-dependent patients as well as afford them the opportunity to experience the physical and psychologic benefits typically associated with cardiac rehabilitation.

Effects of sensor selection on exercise stroke volume in pacemaker dependent patients.

The effects of sensor selection and sensor blending on the cardiovascular response to graded exercise was evaluated in 10 patients (age 74 +/- 2 yrs; 7 men and 3 women) implanted with a dual sensor rate adaptive VVIR pacemaker (Vitatron Topaz model 515). Patients underwent three graded exercise tests (GXT) with sensor programming randomly assigned. For a given graded exercise text the pacemaker was programmed into activity sensing (ACT), QT sensing, or dual sensing (ACT = QT). Data were recorded at rest and during each stage of the graded exercise text. Oxygen uptake (VO2) was measured continuously using a Q Plex I system. Heart rate (HR), stroke volume (SV), and cardiac output (Qc) were measured by impedance cardiography. Systolic time intervals were calculated from simultaneous recordings of the ECG, phonocardiogram, and the impedance cardiogram. In response to the GXT no differences in peak VO2 were observed across the three sensor settings. Regardless of the sensor setting Qc increased linearly with each increment in VO2. The HR response to ACT only pacing was significantly higher than in the other two pacing conditions. During ACT only pacing SV failed to rise in response to exercise. The increased exercise Qc during QT and ACT = QT pacing were mediated by significant increases in both HR and SV. The QT and dual pacing conditions were also associated with longer diastolic filling times. The data indicate that the mechanisms responsible for the increase Qc during exercise were different for ACT versus ACT = QT or QT sensor-driven pacing.

Medtronic mosaic porcine bioprosthesis satisfactory early clinical performance.

BACKGROUND: The Medtronic (Minneapolis, MN) Mosaic porcine bioprosthesis is an investigational prosthesis which incorporates zero-pressure fixation, aortic root predilation, low profile stent, and alpha oleic acid antimineralization treatment. METHODS: From September 1994 to August 1996, 289 patients (mean age 70 years, range, 28 to 88 years) had 227 (78.5%) aortic valve replacements and 62 (21.5%) mitral valve replacements. Concomitant procedures were performed in 61.2% (139) of aortic valve replacements and 54.8% (34) of mitral valve replacements. Of the aortic valve replacement group 70 (30.8%) were in the 61 to 70 age group and 134 (59.0%) were 71 years or older. Of the mitral valve replacements, 23 (37.1%) were 61 to 70 years and 30 (48.4%) 71 years or older. RESULTS: The early mortality, overall, was 4.2% (12 of 289); for aortic valve replacement it was 4.0% (9) and for mitral valve replacement it was 4.8% (3). The late mortality for aortic valve replacement was 2.6% per patient-year (3 events, 1.3% of total) and for mitral valve replacement it was 3.3% per patient-year (one event, 1.6% of total). The reoperative rate for aortic valve replacement was 3.0% per patient-year (4), while there were no mitral valve replacement reoperations. The freedom from major thromboembolism was 97.3%+/-1.6% for aortic valve replacement and 94.7%+/-3.0% for mitral valve replacement at 1 to 1.5 years. The freedom from reoperation was 96.7%+/-1.7% for aortic valve replacement; there was no reoperation for mitral valve replacement. There were no cases of structural valve deterioration. In the aortic position the mean systolic gradient was low, approximately 11 mm Hg, across all sizes (range 8 to 12 mm Hg at 3 months and 10 to 13 mm Hg at 12 months). In the mitral position the mean diastolic gradient was approximately 5 mm Hg (range, 2 to 6 mm Hg) for all sizes 25 to 31 mm at the early and 1 year follow-up echocardiographic assessment. CONCLUSIONS: The early clinical performance and in vivo hemodynamics are encouraging.

Cellular changes in HeLa cells and cervix cells after treatment with cyclic nucleotides.

Determination of tumor cell maturity and induction of cell differentiation are significant issues in oncology. We studied here in vitro the effects of cyclic AMP and cyclic GMP on human cervix carcinoma cells (HeLa cells), using normal human cervix cells as controls. Relative plasma membrane fluidity (which corresponds with the adhesive power of the cell, membrane permeability, and the ability to maintain the ionic milieu), cell cycle characteristics, and protein kinase C activity (a regulator of the cell cycle) were determined. In the untreated HeLa cells, membrane fluidity and protein kinase C activity were increased versus the controls. Administration of dbcAMP decreased the membrane fluidity and the protein kinase C activity, prolonged the G0/G1 phase of the cell cycle and shortened the S + G2 + M phase; with dbcGMP, the opposite changes were recorded (all findings, p < 0.05). Findings from HeLa cells treated with dbcAMP approached those from the normal controls. Each of the parameter studied reflected the differentiation of the HeLa cells during dbcAMP treatment. They may be of potential use for the determination of tumor cell maturity in clinical oncology.

Duke University Longitudinal Studies of Aging.

The Duke Longitudinal Studies of Aging were preceded by a research project supported by the National Institutes of Health and entitled "The Effects of Aging upon the Central Nervous System: A Physiological and Psychological Approach." These earlier studies formed a solid basis for designing and carrying out the two Duke Longitudinal Studies. The Duke longitudinal interdisciplinary research team existed between 1955 and 1980. The first longitudinal study of "normal aging" began in 1955. The subjects were 270 community residents and volunteers aged 60 to 90. Eleven rounds of complete examinations were carried out. The eleventh and final round occurred in 1976. The second Duke Longitudinal Study (also known as the "Adaptation Study") began in 1968 and ended in 1976. The research design was cross-sequential with 502 subjects 46 to 70 years of age. Numerous ancillary studies were conducted on both studies. Both studies included biomedical, psychological, and socioeconomic observations and evaluation procedures. All data are preserved and available for secondary analysis by qualified persons.

Intracellular changes of HeLa cells after single or repeated treatment with cytostatics.

HeLa cells were treated once or repeatedly using the cytostatics doxorubicin (adriamycin, Ad, CAS 23214-92-8), cisplatin (Pt, CAS 15663-27-1) and fluorouracil (FU, CAS 51-21-8). Intracellular GSH (reduced glutathione) contents, activities of protein kinase C, cytotoxicity and membrane fluidity were investigated. During single treatment protein kinase C activities as well as membrane fluidity increased, whereas intracellular GSH decreased. With repeated treatments protein kinase C activities increased further. Membrane fluidity as well as intracellular GSH contents increased. The investigated parameters may be correlated with sensitivity of cells against cytostatics.

[Plasma-membrane fluidity studies of murine neuroblastoma and malignant melanoma cells under irradiation]. / Untersuchungen über die Fluidität der Plasmamembran von murinen Neuroblastom- und malignen Melanomzellen unter Bestrahlung.

Murine neuroblastoma (C-1300 NMB) and malignant melanoma (B16) cells were radiated in presence of radiopharmaceutics. Sensibilization was carried out with BSO and protection with TMX. Changes in fluidity of the plasma membrane, in cellular GSH contents and cell cycle were observed. After radiation fluidity of the plasma membrane is increased, whereas intracellular GSH decreased. These changes were intensified by BSO and reduced by TMX. Fluidity of the plasma membrane correlates with intracellular GSH and also with cell cycle. It is suggested that changes in plasma membrane fluidity can be used as an additional parameter for the determination of sensitivity towards radiation.

Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo.

The influence of alpha-lipoic acid (CAS 62-46-4) on the amount of intracellular glutathione (GSH) was investigated in vitro and in vivo. Using murine neuroblastoma as well as melanoma cell lines in vitro, a dose-dependent increase of GSH content was observed. Dependent on the source of tumor cells the increase was 30-70% compared to untreated controls. Normal lung tissue of mice also revealed about 50% increase in glutathione upon treatment with lipoic acid. This corresponds with protection from irradiation damage in these in vitro studies. Survival rate of irradiated murine neuroblastoma was increased at doses of 100 micrograms lipoic acid/d from 2% to about 10%. In agreement with the in vitro studies, in vivo experiments with whole body irradiation (5 and 8 Gy) in mice revealed that the number of surviving animals was doubled at a dose of 16 mg lipoic acid/kg. Improvement of cell viability and irradiation protection by the physiological compound lipoic acid runs parallel with an increase of intracellular GSH/GSSG ratio.

Non-myelotoxic antitumour effects of L-dopa, buthionine sulphoximine and tamoxifen on neuroblastoma cells in vitro and in vivo.

The effects of three non-myelotoxic cancer drugs on the growth of neuroblastoma cells were investigated in vitro and in vivo: dihydroxyphenylalanine (L-dopa, a drug with selective toxicity for melanoma cells), DL-buthionine sulphoximine (BSO, a drug with radiosensitizing effects), and tamoxifen (a drug used in the treatment of human mammary carcinoma). In vivo these substances significantly reduced the weight of neuroblastoma tumour transplants in the mice (nude/nude) (P less than 0.05). A dose/effect relationship could be established. In vitro, the D50 was determined, using fibroblasts as controls. The growth of neuroblastoma tumours was inhibited by different mechanisms: L-dopa and its metabolite dopamine reduced the activity of tyrosinase, BSO reduced glutathione levels, and L-dopa and tamoxifen raised cAMP concentrations.

Research on the differentiation of human and murine neuroblastoma cells.

In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.

[Change in adenyl cyclase activity in the differentiation of neuroblastoma cells]. / Anderung der Adenylcyclase-Aktivität während der Differenzierung von Neuroblastomzellen.

The change of Adenylcyclase from the plasma membrane of neuroblastoma cells during cell differentiation was investigated. As a parameter for the change of the Adenylcyclase activity we determined the Adenylcyclase stimulatability caused by the neurotransmitters noradrenaline, dopamine and adrenaline. In differentiated neuroblastoma cells the basilar Adenylcyclase activity was higher than in undifferentiated cells. The tested neurotransmitters showed the same result. By means of a G-protein from medullary adrenal gland we succeeded in reconstructing the Adenylcyclase from both undifferentiated and differentiated cells. The importance of the Gs protein for the cell differentiation is discussed.

[In vitro and in vivo effect of thyroid hormones on the growth of neuroblastoma cells. I. The effect of triiodothyronine in vitro]. / In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen. I. Effekt von Trijodthyronin in vitro.

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10(-4) M/10(6) cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

[In vitro and in vivo effect of thyroid hormones on the growth of neuroblastoma cells. II. The effect of thyroxine in vivo]. / In-vitro- und in-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen. II. Effeckt von Thyroxin in vivo.

We studied the effect of thyroxine (T4 0.050 mg/kg/d, i.p.), TSH (0.08 U/kg/d, i.p.) and hypothalamic peptide (HF; 1 mg protein/kg/d, i.p.) given alone or in combination, on the growth of murine (NB C-1300) and human (NB Park) neuroblastoma transplanted onto the nude mouse (nu/nu). Both T4 and TSH caused a significant increase (perchlorate a decrease) of the serum T3. Histologically, the T4 treatment was followed by partial tumor necrosis and a marked growth of connective tissue within the tumors; there was no significant change in tumor weight as compared to the control group. Treatment with HF alone or in combination with T4 inhibited in 30% the invasive growth of the neuroblastoma transplants and a fatty degeneration was found in 25% of the human NB-TX after 28 days of treatment. The measurement of the intratumoral content of the cyclic nucleotides showed a significant increase of the cAMP and a decrease of the cGMP. The morphological and biochemical alteration observed under treatment with thyroid hormone or analogues could possibly be applied for therapeutic purposes.

[Changes in the intracellular concentration of cyclic nucleotides in the differentiation of neuroblastoma cells]. / Veränderungen der intrazellulären Konzentrationen der zyklischen Nukleotide während der Differenzierung von Neuroblastomzellen.

High performance liquid chromatography allows a simultaneous determination of ATP, CTP, GTP, and the cyclic nucleotides. During cell differentiation initiated by DBcAMP, we observed an increase in ATP, cAMP, GTP and an decrease in CTP, cCMP, and cGMP levels. It is being discussed the changes of relation between the triphosphates their corresponding cyclic nucleotides during the differentiation of NB cells.