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Biomedical subjects

I Goetz

Publications and source records attributed to I Goetz.

16 recordsLinked to original sources

Evidence for three distinct classes of 'typical', 'psychotic' and 'dual' mania: results from the EMBLEM study.

OBJECTIVE: To describe patients included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study and to assess and clinically validate the presence of clinical subtypes of patients with acute mania. METHOD: The EMBLEM study is a 2-year prospective, observational study on the treatment and outcome of patients who are treated for a manic or mixed episode. Latent Class Analysis was used to define discrete groups of patients at baseline. RESULTS: Three groups were identified: 'typical mania' (59% of patients); 'psychotic mania' (27%) with more severe mania and presence of psychotic symptoms; and 'dual mania' (13%) with a high proportion of substance abuse. Patient groups differed in age of onset, social functioning and service needs. CONCLUSION: Dual mania represents a distinct and not infrequent subgroup of patients with mania. The exclusion of patients with comorbid substance problems from clinical trials creates a gap in our knowledge on treatment effectiveness.

Adult↗

Assessment of tidal breathing parameters in infants with cystic fibrosis.

Simple methods are needed to assess lung function in infants with cystic fibrosis (CF). This study determined the relationship between simple measurements obtained from tidal breathing with those from more complicated forced expiratory manoeuvres. Healthy infants and infants with CF were recruited from two maternity units and five specialist CF hospitals, respectively. Respiratory rate, tidal volume, minute ventilation and the tidal breathing ratio (TPTEF:TE) were measured in sedated infants and compared with forced expiratory volume in 0.4 seconds (FEV0.4) measured by the raised volume technique. Altogether, 95 healthy infants and 47 infants with CF of similar age, sex, ethnicity and proportion exposed to maternal smoking were recruited. There was no difference in TPTEF:TE and tidal volume between healthy infants and those with CF. Minute ventilation was significantly greater in infants with CF due to a mean (95% confidence interval) increase in respiratory rate of 5.8 (3.2-8.4) min(-1). Thirteen (28%) infants with CF had a respiratory rate elevated by >2 SD. However, no association between respiratory rate and FEV0.4 could be identified. Tidal breathing ratio was not useful in identifying diminished airway function in infants with cystic fibrosis. An elevated respiratory rate may be due in part to ventilation heterogeneity but is poorly predictive of diminished airway function measured by forced expiration.

Child, Preschool↗

Exploring the relationship between forced maximal flow at functional residual capacity and parameters of forced expiration from raised lung volume in healthy infants.

The raised volume rapid thoraco-abdominal compression technique (RVRTC) is being increasingly used to assess airway function in infants, but as yet no consensus exists regarding the equipment, methods, or analysis of recorded data. The aim of this study was to explore the relationship between maximal flow at functional residual capacity (V'(maxFRC)) and parameters derived from raised lung volumes, and to address analytical aspects of the latter technique in an attempt to assist with future standardization initiatives. Forced vital capacity (FVC) from lung volume raised to 3 kPa, timed forced expiratory volumes (FEV(t)), and forced expiratory flow parameters at different percentages of expired FVC (FEF(%)) were measured in 98 healthy infants (1-69 weeks of age). V'(maxFRC) using the tidal rapid thoraco-abdominal compression (RTC) technique was also measured. The within-subject relationships and within-subject variability of the various parameters were assessed. Duration of forced expiration was < 0.5 sec in 5 infants, meaning that FEV(0.3) and FEV(0.4) were the only timed volume parameters that could be calculated in all infants during the first months of life, and even when it could be calculated, FEV(0.5) approached FVC in many of these infants. It is recommended that FEV(0.4) be routinely reported in infants less than 3 months of age. Contrary to previous reports, within subject variability of V'(maxFRC) was less than that of FEF(75) (mean CV = 6.3% and 8.9%, respectively).A more standardized protocol when analyzing data from the RVRTC would facilitate comparisons of results between centers in the future.

Crown-Rump Length↗

The association between birthweight, sex, and airway function in infants of nonsmoking mothers.

The risk of respiratory illness and death is increased in infants of low birthweight for gestational age, but the underlying physiologic mechanisms remain unclear. We examined the hypothesis that airway function is diminished in infants of low birthweight for gestational age, independent of exposure to maternal smoking. Respiratory function was measured using partial and raised volume forced expiratory maneuvers in 103 infants (> 35 wk gestation; 56 boys) not exposed pre- or postnatally to maternal smoking who, according to birthweight, were either small (SGA; n = 38) or appropriate (AGA; n = 65) for gestational age. At testing, SGA infants were of similar postnatal age (mean [SD]: SGA 6.8 [2.4] wk, AGA 5.9 [2.3] wk), but remained shorter and lighter than AGA infants. In univariate analyses, FVC, forced expired volume in 0.4 s (FEV(0.4)), and FEF(75) were significantly diminished in SGA compared with AGA infants (mean [95% CI of difference]: FVC: 127 versus 143 ml [-29, -2]; FEV(0.4): 112 versus 125 ml [-24, -2]; and FEF(75): 173 versus 203 ml s(-1) [-57, -3], respectively), but these differences were no longer significant after allowing for sex and body size. Furthermore, FEF(75) was on average 35 ml s(-1) lower in boys than girls (95% CI: -61, -8). We conclude that diminished airway function in SGA infants shortly after birth appears to be primarily mediated through impaired somatic growth.

Analysis of Variance↗

Influence of jacket placement on respiratory compliance during raised lung volume measurements in infants.

SUMMARY. Recent introduction of the raised lung volume rapid thoraco-abdominal compression (RVRTC) technique for measuring forced expiratory maneuvers in infants provides the potential opportunity to assess respiratory mechanics simultaneously by using multiple linear regression (MLR) of the relaxed breaths preceding jacket inflation to force expiration. This study was undertaken to investigate whether data obtained from raised lung volume are influenced by placement of the rapid thoraco-abdominal compression (RTC) squeeze jacket. Paired measurements of tidal volume (V(T)) and respiratory rate (RR) during tidal breathing, and of inflation volume (V(inf)), respiratory system compliance (C(rs)), and resistance (R(rs)) during passive lung inflations were made in 60 (30 male) healthy term infants with and without a fastened, but uninflated RTC jacket in place. Jacket placement was associated with a significant reduction (P < 0.0001) in weight-corrected V(inf) [-1.86 (95% confidence interval, -2.46, -1.27) mL.kg(-1)] and C(rs) [-0.77 (-1.04, -0.49) mL.kPa(-1).kg(-1)]. This represented a reduction in weight-corrected C(rs) from 9.00 to 8.24 mL.kPa(-1).kg(-1), with the fall being >10% in 42% of infants studied. There was no significant change in R(rs) or weight-corrected V(T). If passive respiratory mechanics are to be measured during raised lung volume maneuvers, they should be performed prior to the jacket being fastened, unless considerable care is taken with each infant to ensure that the jacket does not restrict chest wall movement during maximum inflation.

Airway Resistance↗

Passive respiratory mechanics: the occlusion techniques.

The aim of this position paper is to define quality control and acceptance criteria for measuring passive respiratory mechanics in infants using the occlusion techniques to ensure that valid results are obtained. These guidelines cover numerous aspects including: 1) terminology and definitions; 2) equipment; 3) data acquisition; 4) data handling and analysis; 5) reporting of results. Adherence to these guidelines should ensure that measurement of passive respiratory mechanics in infants in different lung function laboratories could be performed with an acceptable degree of safety, precision, and reproducibility. This will facilitate multi-centre collection of data and performance of clinical investigations.

Airway Resistance↗

Assessment of passive respiratory mechanics in infants: double versus single occlusion?

The single breath or occlusion technique (SOT) is widely used to assess passive respiratory mechanics in infants, but depends on various underlying assumptions. Recently, it has been proposed that such measurements could be internally validated by performing two brief airway occlusions during the same expiration. The aim of this study was to evaluate the use of the double occlusion technique (DOT) using a new commercially available program (Jaeger MasterScreen BabyBody Erich Jaeger GmbH, Würzburg, Germany). Paired measurements of respiratory system compliance (Crs) and resistance (Rrs) using both SOT and DOT were obtained in 18 healthy sedated infants (age range 4-41 weeks, weight 2.7-9.9 kg). There was close agreement between both methods of assessing Crs in all infants, the mean within-subject difference (95% confidence interval (CI)) for DOT-SOT being -0.06 (-0.55- +0.42) mL x kPa(-1) x kg(-1). By contrast, estimates of Rrs,DO were on average 20% lower than those for Rrs,SO, (mean within-subject difference (95% CI) being -0.67 (-1.04- -0.31) kPa x L(-1) x s; p<0.01). The relatively lower values obtained for Rrs,DO may reflect the higher mean lung volume at which it was calculated. Further work is required to investigate the clinical and epidemiological relevance of this new approach, and whether there are any advantages of using both techniques when assessing passive mechanics in infants.

Humans↗

Status of allogeneic bone marrow transplantation in childhood in the GDR.

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.

Adolescent↗

Transplantation of major AB0-incompatible bone marrow: removal of red cells by dextrane sedimentation.

The elimination of erythrocytes by dextran sedimentation is a useful method to prevent haemolytic complications after AB0-incompatible bone marrow transplantation. The procedure presented here lasts only 1.5-2 hours, is high reproducible and safe in respect of infections. The mean recovery of nucleated cells amounted to 94%. The contamination with erythrocytes is low (recovery 1.1%). We have never seen haemolytic reactions during 7 AB0-incompatible bone marrow transplantations.

ABO Blood-Group System↗

Triethanolamine, tris, hepes, and cytosine arabinoside show neuritogenic activity in cultured chick embryo ganglia.

Neuritogenesis, which occurs to a slight extent in chick embryo ganglia maintained under standard conditions and which is maximally stimulated by nerve growth factor, also was enhanced by presence in the medium of buffers (triethanolamine, Tris, and Hepes) and cytosine arabinoside and by the passage of direct electric current. The major effect of the buffers probably was to remove protons from cell membranes, that of the current to produce accelerated movement of ions through membranes of the ganglionic cells, and that of cytosine arabinoside to decrease the numbers of nonneural cells by inhibiting DNA synthesis. The buffers were neuritogenically ineffective on nerve growth factor-sensitive PC12 pheochromocytoma cells in culture. Media from ganglia in which triethanolamine or passage of electric current had elicited outgrowth of neurites produced no observable effect on PC12 cells under our experimental conditions. Current data fit the hypothesis that, whereas nerve growth factor exerts direct neuritogenic effects on neurons, the other treatments affect neural-nonneural interactions, possibly by way of gap junctions or changes in direct physical contact, so as to disinhibit inherent neural neuritogenic potential and/or to stimulate it.

Animals↗

Sex and age alter plasma membranes of cultured fibroblasts.

Human skin fibroblasts were taken from age-matched male and female subjects. The cells were then cultured under identical conditions and passage-number matched. Plasma membranes were isolated and membrane enzyme activities, lipid composition, and structure of isolated plasma membranes were measured in order to determine the presence of significant sex differences in human fibroblast membrane properties. The results indicated that plasma membranes from normal female subjects had a 1.6-fold and 3.6-fold higher cholesterol/phospholipid ratio and oleic acid (18:2) content than normal male subjects. The limiting anisotropy and the rotational relaxation time of fluorescence probe molecules such as trans-parinaric acid and 1,6-diphenyl-1,3,5-hexatriene in the plasma membranes was not significantly different from fibroblasts of male versus female normal subjects. The total activity of plasma membrane (Na+, K+)-ATPase was significantly higher in female than male normal subjects. A potential 'membrane structural disorder', Huntington's disease, was confirmed in fibroblast membranes from male but not from female Huntington's disease subjects. The possibility that Huntington's disease was a 'premature membrane aging' phenomenon was considered. A comparison of plasma membrane enzymes, lipids, and structure from old and young Huntington's disease subjects did not show differences consistent with accelerated membrane aging as explaining the molecular basis for the disease. The age-dependent differences noted in aged Huntington's disease subjects: increased phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin + lysophosphatidylcholine content of fibroblast plasma membranes were not significantly altered when compared to normal age-matched controls. However, (Na+, K+)-ATPase activity was significantly enhanced in fibroblast plasma membranes of older Huntington's disease subjects unlike those of control subjects. In conclusion, sex and age differences in membrane properties of cultured cells represent important potential variables in the elucidation of human genetic disorders that may be membrane-related.

Adult↗

Age-related alterations in cultured human fibroblast membrane structure and function.

Membrane enzyme activities, lipid composition, and fluorescence probe characteristics in isolated plasma membranes, microsomes and mitochondria of cultured human fibroblasts were used to determine if structural alterations occurred as a function of donor age. The cells were sex matched and allowed to undergo approximately 8 population doublings under identical culture conditions. Plasma membrane (Na+, K+)-ATPase, microsomal NADPH cytochrome c reductase, and mitochondrial succinate cytochrome c activities showed variation as a function of increasing donor age but these changes were not statistically significant. At the same time the cholesterol/phospholipid molar ratio was unaltered in plasma membranes, decreased 50% in microsomes, and unchanged in mitochondria with increasing donor age. The phosphatidylcholine/phosphatidylethanolamine ratio increased in all three membrane fractions with increasing age of the fibroblast donor. The ratio of unsaturated/saturated fatty acids decreased in the phospholipids of microsomes but not of plasma membranes or mitochondria. The structural properties of the membranes were determined with two different fluorescence probe molecules, trans-parinaric acid and 1,6-diphenyl-1,3,5-hexatriene. These probe molecules indicated that the fluorescence lifetime and/or fluorescence polarization of the trans-parinaric acid probe decreased in microsomes, mitochondria, and in the plasma membrane, such that the limiting anisotropy, indicative of restrictions to probe motions, was significantly lower (high fluidity) with increasing subject age in plasma membranes, microsomes and mitochondria. The trans-parinaric acid fluorescence lifetime displayed two components in plasma membranes, microsomes, and mitochondria, a finding consistent with the coexistence of fluid and solid membrane lipid areas in the cultured human fibroblast subcellular membranes. The trans-parinaric acid partitioned preferentially into solid membrane areas. The limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene, a fluorescent probe that partitioned almost equally into different lipid domains, was also decreased in microsomes and mitochondria with increasing donor age. In contrast, 1,6-diphenyl-1,3,5-hexatriene indicated a small increase in limiting anisotropy (0.219 vs 0.195) in plasma membranes. Arrhenius plots of trans-parinaric acid and 1,6-diphenyl-1,3,5-hexatriene absorbance-corrected fluorescence in plasma membranes, microsomes and mitochondria demonstrated characteristic breakpoints near 20 degrees C and 30 degrees C. These breakpoints were not altered as a function of age.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Actin filaments in human skin fibroblasts are similar in normal persons and patients with Huntington's disease.

Actin filaments in skin fibroblasts from patients with Huntington's disease (HD) were examined using immunofluorescent methods. Actin filaments were seen along the axis of cell elongation (stress or sheath filaments) as well as in areas of membrane ruffling (lattice filaments). In some cases, filaments appeared to radiate from foci within the cell. Bundles of these filaments radiated in various directions at different depths within a cell. These structures are similar, in cells from both normal individuals and HD patients, to actin filaments observed in other cell types. The higher-than-normal confluent densities achieved in culture by fibroblasts from patients with Huntington's chorea do not involve alterations in the ultrastructure of actin filaments.

Actins↗

Fibroblasts in Huntington's disease.

We investigated the growth of skin fibroblasts in tissue culture from 10 patients with Huntington's disease and eight healthy, unrelated controls. The patients' ages ranged from 34 to 56 years (mean 48.5), and the mean duration of their clinical illness was 12.4 years. The controls' ages ranged from 32 to 64 years (mean, 42.3). No statistically significant differences were observed between the two groups in out-growth of cells from the biopsies nor during subsequent routine culturing of fibroblasts. This contradicts the finding of earlier investigators that skin fibroblasts from patients with Huntington's disease grow poorly in tissue culture. Matched pairs of Huntington's disease and control cultures grew at the same rate, but Huntington's disease cells grew to a significantly higher maximal density (P less than 0.02). This may indicate a genetically determined change in the cell surface or metabolic difference in Huntington's disease.

Adult↗