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Biomedical subjects

J John

Publications and source records attributed to J John.

At least 73 records · Page 4Linked to original sources

[Cost control in public health by rationing--what are the advantages and disadvantages?].

In Germany, the discussion on the pros and cons of rationing health care services in the statutory health insurance funds has just begun, but it will probably be of great importance in the years to come. Until now, it is mainly a political discussion with only very few researches participating. In order to enhance the matter-of-factness in this controversial debate, the experiences in the USA with rationing health care services are summarised, and in the second part a more general discussion is added on different forms and consequences of rationing. The present discussion in Germany is outlined in the third part of the paper. In our own evaluation two arguments are stressed: Firstly, the central argument that rationing of health care services is inevitable because health care costs are "exploding", has as yeb no firm empirical and theoretical basis. Secondly rationing by taking medically useful benefits from the schedule of benefits in the statutory health insurance funds is not compatible with the ethical principles governing these funds.

Cost Control↗

Substrate and product structural requirements for binding of nucleotides to H-ras p21: the mechanism of discrimination between guanosine and adenosine nucleotides.

The interaction of the protein product of the H-ras oncogene with a series of nucleoside di- and triphosphates has been examined to investigate the tolerance of the active site to departures from the GTP or GDP structures. Nucleotides which bind relatively strongly could be used as competitors of GDP in a simple filter binding assay to give semiquantitave estimates of their affinities. For more weakly binding nucleotides or to obtain quantitative data, a transient kinetic method was used which was based on determination of the association and dissociation rate constants. The results obtained indicate that substantial modification of the sugar or phosphate structure is tolerated with little or moderate loss of affinity, but that large losses in affinity occur on modification of the base structure. In particular, replacing the guanine by an adenine residue leads to a dramatic loss of affinity. Thus, discrimination against ATP and ADP is very high (relative affinities of ATP and GTP 1:10(7)). This is due not only to loss of positive (stabilizing) interactions, but especially to the introduction of negative ones.

Acid Anhydride Hydrolases↗

Medial preoptic alpha-2 adrenoceptors in the regulation of sleep-wakefulness.

Adrenergic alpha 2 agonist (clonidine) and its antagonist (yohimbine) were locally applied to the medial preoptic area (mPOA), to find out the role of alpha 2 receptors at this brain region in the regulation of sleep-wakefulness. Clonidine produced arousal, whereas yohimbine induced sleep in freely moving animals. Behavioural arousal produced by clonidine administration was accompanied by EEG synchronization. The alpha 2 receptor as the probable site of action of externally applied norepinephrine (NE), is discussed.

Animals↗

Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation.

The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.

Animals↗

Differentiation of pathogenic Escherichia coli strains in Brazilian children by PCR.

A PCR technique to differentiate pathogenic enteric Escherichia coli strains in a field setting was evaluated. Among 76 children with acute diarrhea, this technique identified 12 children (16%) with enterotoxigenic E. coli, 6 (8%) with enteropathogenic E. coli, and 1 (1%) with enteroinvasive E. coli infection. Compared with the conventional assays, the PCR method proved to be simpler, more rapid, and inexpensive and therefore suitable for application in a developing-country field setting.

Bacteriological Techniques↗

Dynamics of carbon dioxide elimination following ventilator resetting.

BACKGROUND: Carbon dioxide elimination (VCO2) at steady state corresponds to the metabolic rate. A change in tidal ventilation will lead to a transient response in VCO2 if other determinants of VCO2 are constant. This principle may be applied in the critical care unit to reset ventilators. OBJECTIVE: To define and characterize the transient response of VCO2 to a well-defined change in ventilation. METHODS: Forty-four patients in stable condition receiving volume-controlled mechanical ventilation had trend recordings of ventilator pressures, flow, volumes, VCO2, and end-tidal CO2 (ETCO2) for 20 min. At time t0, the minute ventilation was either increased (n = 22) or decreased (n = 22) by 10% after which these parameters were monitored over 30 min. Blood gas values were measured 5 and 20 min after the change in ventilation and the dead space fractions were computed using the single breath-CO2 test. DATA ANALYSIS: The first ten breaths (till t1) after a change in ventilation were excluded. The time constant (tau) of the relative change in VCO2 (delta VCO2) was calculated by fitting exponential regressions to delta VCO2 for periods up to 20 min after t1. RESULTS: The delta VCO2 at t1 was proportional to the relative change in tidal volume (delta VT). The proportionality decreased gradually during 20 min. The proportionality of the relative change in ETCO2 (delta ETCO2) or PaCO2 (delta PaCO2) with delta VT was minimal at t1 and increased during the 20 min. tau increased progressively when calculated over longer periods (p < 0.001). tau was similar in the groups with increased and decreased ventilation up to 5 min, after which it was longer in the group with decreased ventilation (p < 0.05). The delta PaCO2 after 20 min correlated best with delta VCO2 at t1 (r = -0.8) and with delta ETCO2 at the end of 20 min (r = 0.8). CONCLUSIONS: Noninvasively monitored VCO2 provides an instantaneous indication of the change in alveolar ventilation in well-sedated, mechanically ventilated patients in stable condition without significant cardiopulmonary disease.

Adult↗

Effect of application of gamma amino butyric acid at the medial preoptic area on sleep-wakefulness.

Intracerebral microinjections of gamma amino butyric acid were given bilaterally at the medial preoptic area (mPOA) to determine the possible role of this neurotransmitter in the genesis and regulation of sleep-wakefulness. GABA (50 micrograms/0.2 microliters) when administered through chronically implanted cannulae in free moving rats, did not produce any significant alterations in sleep-wakefulness. This may be attributed either to the non-involvement of GABA at the level of mPOA in the regulation of sleep, or to other factors like the low dose and rapid breakdown of the injected drug.

Animals↗

Advertising in dentistry--a position paper.

The limitations on advertising set by current regulations are examined and the possible consequences of relaxing these regulation discussed. The opinions of the dental profession on this issue, as determined through a questionnaire survey of members of the Singapore Dental Association (SDA), are included. Finally, some recommendations are made with respect to modifying current advertising laws.

Advertising↗

The crystal structure of glucose dehydrogenase from Thermoplasma acidophilum.

BACKGROUND: The archaea are a group of organisms distinct from bacteria and eukaryotes. Structures of proteins from archaea are of interest because they function in extreme environments and because structural studies may reveal evolutionary relationships between proteins. The enzyme glucose dehydrogenase from the thermophilic archaeon Thermoplasma acidophilum is of additional interest because it is involved in an unusual pathway of sugar metabolism. RESULTS: We have determined the crystal structure of this glucose dehydrogenase to 2.9 A resolution. The monomer comprises a central nucleotide-binding domain, common to other nucleotide-binding dehydrogenases, flanked by the catalytic domain. Unexpectedly, we observed significant structural homology between the catalytic domain of horse liver alcohol dehydrogenase and T. acidophilum glucose dehydrogenase. CONCLUSIONS: The structural homology between glucose dehydrogenase and alcohol dehydrogenase suggests an evolutionary relationship between these enzymes. The quaternary structure of glucose dehydrogenase may provide a model for other tetrameric alcohol/polyol dehydrogenases. The predicted mode of nucleotide binding provides a plausible explanation for the observed dual-cofactor specificity, the molecular basis of which can be tested by site-directed mutagenesis.

Alcohol Dehydrogenase↗

Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy.

Based on clinical observations, we hypothesized that prolonged parenteral nutrition (in contrast to enteral nutrition) is detrimental after major hepatic resection. Male Sprague-Dawley rats (300 to 380 g) anesthetized with intraperitoneal sodium pentobarbital had 70% hepatic resection and jugular vein and gastrostomy catheterizations using aseptic techniques and were divided randomly into three groups: (1) total parenteral nutrition (TPN) (nutrients via central vein), (2) total enteral nutrition (TEN) (identical nutrients via gastrostomy), and (3) standard oral feeding (SOF) (chow and water ad libitum). Unused catheters were plugged. In the first set of experiments (n = 42), nutrient intake was formulated to approximate the nutritional intake of normal rats, 216 kcal/kg/d. Infusate was 15% glucose, 4.5% amino acids, electrolytes, trace minerals, vitamins, and 20% fat emulsion given half-strength the first day, three-fourths strength the second day, and full strength thereafter. On postoperative day 7, surviving rats were killed. Mortality prior to day 7 was very high (68%) in the TPN group and low in the TEN (9%) and SOF (9%) groups (p < 0.005). Among survivors, the serum albumin level was lowest (p < 0.002) and serum bilirubin level (p < 0.025) and wet weight of regenerated liver (p < 0.002) highest in the TPN group. However, the livers in TPN rats appeared pale and were found to be abnormal histologically with markedly diminished glycogen and amphophylic hepatocyte cytoplasm, and their spleens were enlarged (by a factor of two). The high mortality of TPN rats was seen whether the fat emulsion was given as a bolus daily, continuously as part of the infusate, or not included as part of the TPN regimen. In the next series (n = 70), nutrient concentrations, volumes, and rates of infusion were varied. There was a high correlation between caloric (r2 = 0.831, p < 0.0006), glucose (r2 = 0.598, p < 0.02), and amino acid (r2 = 0.619, p < 0.03) intakes and mortality in the TPN group: at 140 kcal/kg/d, none died; at 178 kcal/kg/d, 50% to 62% died; and at 230 kcal/kg/d, 80% died. No TEN rat died. In conclusion, 70% hepatectomized rats fed enterally with nutrients approximating the intake of normal rats do well and survive. In sharp contrast, mortality is very high when identical nutrients are infused parenterally. By reducing the levels of nutrients given parenterally, survival improves significantly.

Animals↗

Airway and body surface sensors for triggering in neonatal ventilation.

Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (> 40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100 ms even for airway sensors.

Airway Resistance↗

Effect of detergent on alveolar particle clearance due to large tidal ventilation.

BACKGROUND: It has recently been shown that large tidal volume ventilation accelerates the alveolar clearance of insoluble particles and this may be related to accelerated surfactant evacuation from the alveolus into the airway. The aim of this study was to investigate if the effect of large tidal volume ventilation is modified in an experimental model of surfactant dysfunction. METHODS: Fluorescent latex particles of 0.63 microns diameter were administered in aerosol form to 30 rabbits during anaesthesia with thiopentone and mechanical ventilation. Six animals were killed immediately after aerosol administration in order to show the initial deposition of particles. Twenty four animals were divided into two groups and ventilated for three hours with either large tidal volume (mean tidal volume 30 ml/kg) or conventional ventilation (mean tidal volume 12.5 ml/kg). Six rabbits in each of the two groups were administered either the synthetic detergent dioctyl sodium sulphosuccinate in aerosol form or aerosolised vehicle. After the period of experimental ventilation the lungs were removed and dried in the expanded state. Particles in the alveolar region were counted with fluorescent microscopy in sections of the lung. RESULTS: Compared with the baseline group (mean (SD) 24.8 (9.9)) the count of residual alveolar particles was lower after large tidal volume ventilation in the absence of detergent aerosol (13.2 (6.5)). Particle count after large tidal volume ventilation and detergent treatment (23.3 (6.4)) was similar to that in the baseline group and to that in the groups exposed to conventional ventilation. CONCLUSIONS: The increase in alveolar clearance of insoluble particles caused by large tidal volume ventilation is inhibited by detergent aerosol. This might be due to reduced stability of the surfactant film after detergent aerosol.

Aerosols↗

Tidal volume and alveolar clearance of insoluble particles.

We studied the effect of 3 h of large tidal volume ventilation on alveolar clearance of 0.63-micron fluorescent latex particles in rabbits during pentobarbital anesthesia. After particle deposition, six animals were killed as controls, six were subjected to large tidal volume ventilation with a peak pressure of 27 cmH2O, and six were subjected to conventional ventilation with a peak pressure of 11 cmH2O. Mean tidal volumes were 30.2 +/- 6.1 and 8.4 +/- 1.6 ml/kg in the large tidal volume and conventional groups, respectively. End-expiratory pressure was 2 cmH2O in all groups. Compliance decreased only after large tidal ventilation (P = 0.0036). Compared with controls the conventional ventilation group showed no alveolar clearance, but more particles were clustered within macrophages (P = 0.01). Compared with other groups the large tidal volume group had fewer alveolar particles (P = 0.0005), most of which were single particles. Accordingly, large tidal volumes enhance alveolar particle clearance, which is possibly related to distension-related evacuation of surfactant to proximal airways. Clearance may be due to accelerated motion of the particle-loaded macrophage in response to the fast film motion. Alternatively, single particles embedded in the surfactant film may be dragged by the fast-moving film toward the airways.

Animals↗

Dynamic properties of body plethysmographs and effects on physiological parameters.

A model incorporating compliance, resistance, inertia, and the thermal time constant of plethysmographs is used to describe the effect of its dynamic properties on measured respiratory parameters. Using numerical simulation we studied the effect of distortion of flow signals from 13 infants in whom flow and esophageal pressure had been recorded. The distortion in amplitude, shape, and timing of the recorded flow patterns was dependent on the dynamic properties of the plethysmograph. For constant-volume "pressure" plethysmographs, errors of derived parameters such as compliance and resistance are very important if the thermal time constant is short. These errors are not corrected by calibrating the plethysmograph at the breathing frequency. Time correction of the flow signals in volume-displacement plethysmographs gives accurate results when the plethysmograph resistance and compliance are low. Overall, a volume-displacement plethysmograph with moderately high resistance of the flowmeter, corrected for internal pressure and inertia, gives the best possible results.

Air Pressure↗

Biexponential pulmonary clearance of 99mTc-DTPA induced by detergent aerosol.

We measured the pulmonary clearance of technetium-99m-labeled diethylenetriamine pentaacetatic acid (99mTc-DTPA) for 3 h after perturbation of the surfactant system by administration of the detergent dioctyl sodium sulfosuccinate in aerosol. Forty-two rabbits were anesthetized with pentobarbital sodium. Tracheostomies were performed, and the rabbits were mechanically ventilated. Increasing concentrations of detergent (0.125-2%) or vehicle were given for 5 min, and clearance measurements were performed immediately or 60 min after detergent administration. No animals developed respiratory distress. After vehicle, the clearance was monoexponential with a half-life of 153 min. Detergent induced a biexponential clearance with a rapidly clearing additional pool of radioactivity with a half-life of 5-15 min. The relative amount of radioactivity clearing rapidly increased with detergent concentration. The detergent effect was partly reversible. We conclude that detergent induces a biexponential clearance of 99mTc-DTPA by accelerating the transfer of tracer across the alveolocapillary barrier in a proportion of lung units in a dose-related manner.

Aerosols↗

Changes in sleep-wakefulness after kainic acid lesion of the preoptic area in rats.

The role of the preoptic area (POA) neurons in the regulation of sleep-wakefulness (S-W) has been investigated in this study. The cell-specific neurotoxin, kainic acid (KA), was injected (0.8 microgram in 0.2 microliter) intracerebrally for lesioning of the POA. S-W was assessed (on the basis of EEG, EMG, and EOG recordings) for a day before bilateral lesion of the POA, and for 3 weeks after the lesion. There was an increase in wakefulness, and a decrease in all the stages of sleep after KA lesion of the POA. The reduction in deep slow wave sleep (S2) and REM sleep (PS) were more marked than light slow wave sleep (S1), and these had not shown any recovery even after 3 weeks of lesion. Two days after the lesion, the reduction in sleep was much more marked during the daytime than at night. There was an increase in locomotor activity, especially during the daytime, though it was only statistically significant on the 6th and the 10th day after the lesion. This study shows that the POA neurons are involved in the induction and maintenance of sleep. The lesion did not have a long lasting effect on the circadian distribution of sleep but the changes in locomotor activity seem to persist for a longer period.

Animals↗

Referent opinion and health care satisfaction.

The author examines the influence that referent opinion--one's own opinion and the recommendations of relevant others--has on patient perceptions of the quality of care they receive at hospitals. A study of discharged hospital patients reveals that the demographic profile of a patient also has a mediating influence on this effect. Hospital administrators are urged to pay close attention to the relationship between types of referents patients use and how they form their evaluations.

Adult↗

[Toward a European health reporting system--starting points and developmental perspectives].

This article first offers a brief introduction to the development of the EC health policy mandate from a competence restricted to health protection at the working place to a wider competence embracing health promotion and disease prevention, albeit still based on the principle of self-responsibility of the Member states. Possible focal points of health reporting within the EC framework are worked out on the basis of suggestions made by the EC commission in respect of priority areas of EC activities in the public health sphere and the commission's own priority criteria. It is then examined whether and to what extent the presently available health databases (especially of WHO and OECD) would cover these requirements. As a result, it is argued, that there is no getting around setting up an own health reporting system that would promote and support the development of an EC public health policy. An important task of such health reporting will be to supply users not only with data but also with adequate knowledge on how to interpret them, in view of the multitude of problems involved in bringing the various national health data under one roof; this cannot be achieved either at short notice or on a medium-term basis. Finally, a few alternatives are given in respect of possible organisational structures of EC health reporting, pointing out decision criteria and practical conditions which would be essential of assessing the usefulness of such organisational setups.

Disease Notification↗