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M Falk

Publications and source records attributed to M Falk.

At least 19 recordsLinked to original sources
PubMed2002

The 3D structure of human chromosomes in cell nuclei.

The spatial arrangement of some genetic elements relative to chromosome territories and in parallel with the cell nucleus was investigated in human lymphocytes. The structure of the chromosome territories was studied in chromosomes containing regions (clusters) of highly expressed genes (HSA 9, 17) and those without such clusters (HSA 8, 13). In chromosomes containing highly expressed regions, the elements pertaining to these regions were found close to the centre of the nucleus on the inner sides of chromosome territories; those pertaining to regions with low expression were localized close to the nuclear membrane on the opposite sides of the territories. In chromosomes with generally low expression (HSA 8, 13), the elements investigated were found symmetrically distributed over the territories. Based on the investigations of the chromosome structure, the following conclusions are suggested: (1) Chromosome territories have a non-random internal 3D structure with defined average mutual positions between elements. For example, RARalpha, TP53 and Iso-q of HSA 17 are nearer to each other than they are to the HSA 17 centromere. (2) The structure of a chromosome territory reflects the number and chromosome location of clusters of highly expressed genes. (3) Chromosome territories behave to some extent as solid bodies: if the territory is found closer to the nuclear centre, the individual genetic elements of this chromosome are also found, on average, closer the centre of the nucleus. (4) The positions of centromeres are, on average, nearer to the fluorescence weight centre of the territory (FWCT) than to genes. (5) Active genes are not found near the centromeres of their own territory. A simple model of the structure of chromosome territory is proposed.

Cell Compartmentation↗
PubMed2001

Field management of avalanche victims.

The median annual mortality from snow avalanches registered in Europe and North America 1981-1998 was 146 (range 82-226); trend stable in Alpine countries (r=-0.29; P=0.24), increasing in North America (r=0.68; P=0.002). Swiss data over the same period document 1886 avalanche victims, with an overall mortality rate of 52.4% in completely-buried, versus 4.2% in partially-, or non-buried, persons. Survival probability in completely-buried victims in open areas (n=638) plummets from 91% 18 min after burial to 34% at 35 min, then remains fairly constant until a second drop after 90 min. Likewise, survival probability for completely-buried victims in buildings or on roads (n=97) decreases rapidly following burial initially, but as from 35 min it is significantly higher than that for victims in open areas, with a maximum difference in respective survival probability (31% versus 7%) from 130 to 190 min (P<0.001). Standardised guidelines are introduced for the field management of avalanche victims. Strategy by rescuers confronted with the triad hypoxia, hypercapnia and hypothermia is primarily governed by the length of snow burial and victim's core temperature, in the absence of obviously fatal injuries. With a burial time < or =35 min survival depends on preventing asphyxia by rapid extrication and immediate airway management; cardiopulmonary resuscitation for unconscious victims without spontaneous respiration. With a burial time >35 min combating hypothermia becomes of paramount importance. Thus, gentle extrication, ECG and core temperature monitoring and body insulation are mandatory; unresponsive victims should be intubated and pulseless victims with core temperature <32 degrees C (89.6 degrees F) (prerequisites being an air pocket and free airways) transported with continuous cardiopulmonary resuscitation to a specialist hospital for extracorporeal re-warming.

Cardiopulmonary Resuscitation↗
PubMed2001

Phototesting based on a divergent beam--a study on normal subjects.

In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

Adult↗
PubMed2001

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

UNLABELLED: We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

Adolescent↗
PubMed2001

Longitudinal changes of sensitization to farming-related antigens among young farmers.

BACKGROUND: We have shown previously that the prevalence of allergic sensitization in Tyrolean farming students is high, with a clear relationship to occupational exposure. OBJECTIVES: It was the aim of this investigation to assess longitudinal changes in sensitization and a possible impact on lung function. METHODS: Of the 147 farming students in the original cohort, we could re-examine 42 after a mean interval of 4.0 years. All individuals completed a questionnaire and had spirometry, skin prick tests, total and specific IgE analysis, and testing for precipitating antibodies. RESULTS: As compared to the first study, there was a decrease in the frequency of IgE-mediated allergy (30.1 vs. 54.8%; p < 0.05) and in total serum IgE levels (107.4 +/- 254 vs. 157.8 +/- 304 U/ml; p < 0.001). Conversely, 3 individuals had developed precipitating antibodies de novo, and those who had initially had a positive precipitin test (n = 6) were still positive. A larger-sized estate, the lack of a hay dryer, and the presence of moldy hay were confirmed as risk factors for allergic sensitization. Although there was a slight overall decrease in forced vital capacity, no new cases of occupational lung disease were found. CONCLUSIONS: In young Tyrolean dairy farmers, the prevalence of precipitins is constantly high and rising while IgE-mediated allergy declines. Within 4 years, no clinically relevant impact of allergy on lung function was noticed.

Adolescent↗
PubMed2000

Predicting survival infants ventilated with high-frequency oscillation.

UNLABELLED: This retrospective study identifies factors which may predict outcome in preterm infants and infants born at term, ventilated with high-frequency oscillation (HFO). In a 16-bed neonatal and paediatric intensive care unit (level III), 58 consecutive preterm and term infants with a median gestational age of 30 (24-41) weeks and a median birth weight of 1200 (520-3660) g suffered respiratory failure and were managed with HFO as rescue therapy. Forty-nine patients (84%) received exogenous surfactant before HFO which was initiated after a median interval of 20 (1-910) hours following birth. The overall survival rate was 70%. No significant differences existed between survivors and nonsurvivors in respect to demographic data. A greater proportion of patients with respiratory distress syndrome survived (76%) than with lung hypoplasia (20%) or with air-leak syndromes (pulmonary interstitial emphysema 60%, pneumothorax 28%). In survivors, the mean oxygenation index (OI) before HFO was significantly lower than that in nonsurvivors (16 +/- 1.3 vs. 26 +/- 3, p < 0.01) and showed a significant reduction of 32% within 4 hours. In contrast, mean OI increased to 68% over the first 4 hours in nonsurvivors and the difference between survivors and nonsurvivors remained significant during this time (after 2 hours: 15 +/- 1.5 vs. 30 +/- 6, p < 0.01; after 4 hours: 11 +/- 1 vs. 43 +/- 1, p < 0.01). A receiver of operator analysis revealed that an initial OI < 25 or alveolar-arterial oxygen difference (AaDO2) < 450 mmHg predicted survival with a sensitivity of 93% and a specificity of 41%. The positive predictive value was 79%; the negative predictive value, 70%. CONCLUSION: A low OI and AaDO2 at the beginning of HFO, improvement in oxygenation over the first four hours of HFO ventilation and no development of air-leak syndromes were associated with a high predicted survival. This allows early identification of infants who may not survive and may benefit from established and alternative modes of respiratory support such as extracorporeal membrane oxygenation, nitric oxide and liquid ventilation.

Female↗
PubMed1999

Validation of a mail questionnaire for parkinsonism in two languages (German and Italian).

As part of a larger epidemiological study [Neuro-Epidemiology Project South-Tyrol (NEPT)], we investigated the accuracy of a mail questionnaire for parkinsonism in two languages (German and Italian). We administered the instrument to 40 randomly selected subjects with parkinsonism (Italian-speaking, n = 20; German-speaking, n = 20), attending our Parkinson's disease clinic regularly. Each patient was matched by age, sex and language with a subject without parkinsonism residing in the same South-Tyrol Province in Northern Italy. Subjects free of parkinsonism were recruited randomly from two group practices collaborating in the NEPT study. A questionnaire containing nine symptom questions and two additional questions about the patient's diagnosis of parkinsonism and/or treatment was mailed to each subject's home. Forty subjects with parkinsonism and 36 without parkinsonism participated in the study. All nine symptom items showed significant differences between affected and unaffected individuals. A combination of any three questions yielded the best balance between sensitivity (95%) and specificity (89%). There were no differences between the German- and Italian-speaking groups. We demonstrated the usefulness of a simple questionnaire for validating the diagnosis of parkinsonism irrespective of the primary native language.

Adult↗
PubMed1999

Comparison of resin-bonded prosthesis groove parallelism with the use of four tooth preparation methods.

STATEMENT OF PROBLEM: A precise preparation is required to develop resistance form resulting in mechanical stability of the framework for resin-bonded prostheses (RBPs). PURPOSE: The effects of 4 methods of tooth preparation (freehand, guiding pin, extraoral parallelometer, and intraoral parallelometer) on the deviation of proximal grooves from a preestablished path of insertion (guide planes) were investigated under clinical conditions. MATERIAL AND METHODS: Tooth preparation of proximal grooves was performed by 32 dentists on resin substitutes of posterior segments intraorally with a single test patient. A Latin-square randomized cross-over design was selected as the experimental design. RESULTS: The significant least angular deviation of proximal grooves from path of insertion was achieved with an intraoral parallelometer (mean +/- SD 3.15 +/- 1.67 degrees). Compared with freehand tooth preparations (4.37 +/- 2. 11 degrees), neither use of a guiding pin (4.10 +/- 1.62 degrees) nor an extraoral parallelometer (5.06 +/- 2.33 degrees) improved the results. CONCLUSION: Divergence of guiding grooves from path of insertion was reduced with the use of an intra-oral parallelometer. This should improve mechanical stability of posterior RBPs.

Acrylic Resins↗
PubMed1999

Restricted distribution of laminin alpha1 chain in normal adult mouse tissues.

The distribution of laminin alpha1 chain in adult mouse tissue was determined by immunofluorescence using monoclonal antibody 200, reacting with the globular carboxyterminus E3 fragment of alpha1 chain. Strong reactivity was noted only in a few tissues. Reactivity was restricted to epithelial basement membranes. Expression was noted in several epithelial basement membranes of the urinary tract, and male and female reproductive organs. In addition, expression was seen in some parts of the nervous system. Expression was seen in pia mater which surrounds the brain, and in the extracellular matrices covering the vitreous chamber and the lens of the eye. Staining was seen in the adrenal gland cortex, with strongest staining in the zona glomerulosa. Staining was negative in all other studied epithelial basement membranes, such as the lung (trachea or lung epithelium), epidermis, and all parts of the gastrointestinal tract (liver, gut) except for weak staining in the ventricle and Brunner's glands. No expression was seen in basement membranes of fat, Schwann, or endothelial cells in any studied parts of the body. Both small- and large-size vessel walls were negative both in endothelial basement membranes and blood vessel walls, with the exception of some larger brain blood vessels in locations where epithelial cells have invaginated. Neither smooth muscle, myocardium or striated muscle expressed alpha1 chain. We conclude that alpha1-containing heterotrimers including laminin-1 (alpha1beta1gamma1) have a very restricted tissue distribution.

Animals↗
PubMed1999

Leukaemia-associated immunophenotypes (LAIP) are observed in 90% of adult and childhood acute lymphoblastic leukaemia: detection in remission marrow predicts outcome.

Analysis of differentiation antigens on leukaemic blasts is routinely done for diagnostic purposes, i.e. determination of stage of differentiation and lineage assignment. Acute lymphoblastic leukaemias are also frequently characterized by a leukaemia-associated immunophenotype (LAIP), either the coexpression of differentiation antigens physiologically restricted to other stages of differentiation (asynchronous LAIP) or cell lineages (aberrant LAIP). We defined LAIP in 241 consecutive unselected B-lineage (n = 193) and T-lineage (n = 48) ALL by three-colour flow cytometry using directly conjugated monoclonal antibodies. The incidence of LAIP was found to be 91.7%. In 63% of patients two to six leukaemia-associated expression patterns were detected. In order to study the specificity of LAIP in a therapy-relevant setting, remission bone marrow samples from patients with B-lineage ALL were analysed for the expression of T-lineage-associated phenotypes on the normal bone marrow cells and vice versa. The frequency of all T-lineage LAIP+ cells and all aberrant B-lineage LAIP+ cells was <1% in regenerating bone marrow samples at different timepoints. The incidence and clinical significance of LAIP+ cells was studied in 196 remission marrows of 70 ALL patients (55 remaining in CCR, 14 with bone marrow relapse, one with isolated CNS relapse). The presence of >1% LAIP+ at two consecutive timepoints predicted 5/8 bone marrow relapses in B-lineage ALL. The occurrence of LAIP+ cells >1% in T-lineage ALL after induction therapy predicted relapse in 7/7 cases. In conclusion, flow cytometric detection of LAIP+ cells appears to be a powerful tool for the prediction of outcome in ALL.

Adolescent↗
PubMed1998

Laminin isoforms and epithelial development.

Several different approaches suggest that basement-membrane assembly is important for epithelial development. Basement membranes contain isoforms of collagen IV, proteoglycans, and noncollagenous glycoproteins such as the laminins and nidogens. The expression and role of laminins for epithelial morphogenesis is reviewed. Laminins are large heterotrimeric proteins composed of alpha, beta, and gamma chains. Many major epithelial laminins and their receptors have been identified recently, and the extracellular protein-protein interactions that drive basement-membrane assembly are beginning to be understood. Three laminin alpha-chains are typically made by epithelial, alpha 1, alpha 3, and alpha 5. Three major epithelial heterotrimers can at present be distinguished--laminin-1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), and laminin-10 (alpha 5 beta 1 gamma 1)--but other heterotrimers may exist in epithelia. Laminins containing either alpha 1 or alpha 3 chains are largely limited to epithelia, whereas the alpha 5 is also found in endothelial and muscle basement membranes, particularly in the adult. Some epithelial cell types express several laminin alpha-chains, so it is relevant to test how the different laminins affect epithelial cells. Laminins interact with integrin type of receptors on the cell surface, but binding to other proteins has also recently been demonstrated. Two important recent discoveries are the identification of dystroglycan as a major laminin receptor in muscle and epithelia, and nidogen as a high-affinity laminin-binding protein important for basement-membrane assembly. Antibody perturbation experiments suggest that these protein-protein interactions are important for epithelial morphogenesis.

Animals↗
PubMed1998

Transitional cell carcinoma in renal transplant recipients: the influence of compound analgesics.

OBJECTIVES: To determine the incidence of transitional cell carcinoma (TCC) in a renal transplant population and to compare the pattern of neoplasia in patients with analgesic nephropathy (AN) with that in other patients. PATIENTS AND METHODS: Using the Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients of the Princess Alexandra Hospital with TCC were identified. They were separated into two groups based on their primary disease, i.e. AN (group 1) and other causes of renal failure (group 2). The age at diagnosis of TCC, site, grade, stage of TCC and outcome were then compared between the groups. RESULTS: There were 250 (15%) patients in group 1 and 1424 (85%) in group 2; seven patients in each group were found to have TCC, which thus occurred more frequently in the AN group (2.8%) than in group 2 (0.49%). In group 1, five patients died, four from metastatic disease; of these, the mean time from transplantation to diagnosis of the initial tumour was 4.4 years, with a mean time from diagnosis to death of 9 months. In contrast, there were no deaths from metastatic disease in group 2. In group 1, all patients had upper tract tumours, with five patients also having bladder involvement. The upper tract tumours tended to be of a high stage and grade (grade II-III) and were aggressive. In group 2, all the tumours were confined to the bladder and tended to be of low stage and grade (grade I-II Ta). CONCLUSIONS: Patients undergoing renal transplantation as a result of AN are at high risk of developing TCCs of the upper urinary tracts. These tumours tend to be of a high grade and stage and the patients have a poor outcome. Screening with urine analysis and voided urine cytology do not appear to be reliable for the early diagnosis of upper renal tract TCCs in the renal transplant patient. We advocate annual cystoscopy and retrograde ureteric catheterization with washings, brushings and radiological imaging to diagnose upper tract TCCs at an early stage. These patients should also be screened before transplantation using the same technique.

Adult↗
PubMed1998

Release of prostaglandin D2 by murine mast cells: importance of metabolite formation for antiproliferative activity.

Prostaglandin (PG) D2, PGJ2 and delta12-PGJ2 are antiproliferative eicosanoids. We investigated the production of PGD2 by murine bone marrow-derived mast cells (BMMC) taking into consideration metabolism of PGD2 to PGD2 and delta12-PGJ2. PG-metabolites were quantified by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). Stimulated with calcium ionophore A23187 BMMC released eight-fold more PGJ2 and delta12-PGJ2 than PGD2. Conversion of endogenously produced PGD2 to PGJ2 and delta12-PGJ2 proceeded rapidly in contrast to metabolism of exogenously added PGD2. The antiproliferative potency of these prostaglandins is demonstrated in vitro. We conclude that determination of PGD2 production by mast cells must take into consideration rapid conversion to active derivatives, which may play a significant role in growth regulation.

Animals↗
PubMed1998

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Adolescent↗