Respiratory technologists in the frontlines against COVID-19.

Background: The COVID-19 pandemic overwhelmed healthcare resources globally, but especially those of resource-limited countries. Strategies to supplement the number of healthcare workers attending COVID-19 patients had to be implemented. Several institutions used non-respiratory clinicians to work in COVID-19 wards. At Universitas Academic Hospital (UAH), Bloemfontein, South Africa, respiratory technologists were requested to assist with managing the oxygen supportive care of patients with severe COVID-19 and respiratory failure. Objectives: To highlight the contribution that respiratory technologists made in the management of severe COVID-19 pneumonia patients by describing the baseline characteristics and mortality of patients with COVID-19, whose oxygen supportive care was managed primarily by respiratory technologists at UAH. Methods: This was a retrospective study. The investigators extracted data from the hospital files of all adult patients admitted with severe COVID-19 to UAH and where respiratory technologists were involved in their care between 1 January and 31 December 2020. Results: A total of 781 patients were admitted to UAH, of whom 106 fulfilled the inclusion criteria. The majority of the patients were female (n=68; 64.1%), and the median age (interquartile range (IQR)) was 59.5 (51 - 68) years. Hypertension (n=69; 65.1%) and diabetes mellitus (n=39; 36.8%) were the most frequent comorbidities. At the time of admission, the median oxygen saturation was 92% and the median respiratory rate oxygenation (ROX) index was 3.2. The median length of stay was 7 days and the mortality was 41.5%. Conclusion: The clinical characteristics and mortality of patients whose oxygen support was managed by respiratory technologists were similar to those in previously reported studies from resource-limited settings. Respiratory technologists can form a valuable addition to the front-line team when clinicians and nurses are faced with overwhelming patient numbers in subsequent COVID-19 surges and where the mainstay of treatment is oxygen supportive care.

For Debate: Personalized Health Care: As Exemplified by Home Sodium Measurements in a Child with Central Diabetes Insipidus and Impaired Thirst Perception.

BACKGROUND: We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance. METHODS: In order to provide better self-reliance, home point of care testing (POCT) sodium measurement was introduced. RESULTS: Realizing POCT sodium measurement resulted in a significant decrease of ER visits and clinical admissions due to dysregulation of fluid balance. CONCLUSION: This case is an example of personalized health care and has led to better self-reliance and quality of life.

Responsible use of cone beam computed tomography: minimising medico-legal risks.

This communication highlights some of the ethical and possible legal responsibilities which pertain to the taking, reading, reporting, and communication of findings from cone-beam computed tomography (CBCT) scans. The importance of knowledge of head and neck anatomy and pathology to reduce the likelihood of incorrect interpretation is emphasised. Failure to detect critical findings in any diagnostic image can potentially result in medico-legal consequences. CBCT is no exception to this rule. Dental schools are advised to include CBCT imaging as a diagnostic tool in their under- and postgraduate curricula thereby equipping graduates to use 3D imaging in general and CBCT in particular. Existing dental practitioners are advised to seek continuing education on 3D imaging as part of their required lifelong learning.

A previously healthy 11-year-old girl with behavioural disturbances, desquamation of the skin and loss of teeth.

An 11-year-old girl was admitted with backpain, weight loss, fatigue and behavioural disturbances, starting seven weeks before admission. Physical examination showed acrodynia, tremor, cachexia, hypertension and extensive gingival ulceration. Routine laboratory tests were normal, except for a CRP of 98 mg/l. Screening tests for recreational drugs as well as antibody assays for HIV, hepatitis B and borrelia burgdorferia were negative. Chest X-ray, brain CAT and MRI scan were all normal. Lumbar puncture didn't show any abnormalities. Eventually a 24-hour urine test confirmed the diagnosis that was suspected by further questioning.

EEG findings in an eleven-year-old girl with mercury intoxication.

An 11-year-old female was seen at our outpatient clinic with a broad variety of symptoms that were due to elemental mercury intoxication. Electromyography and sequential electroencephalography findings obtained at days 2, 36, 88 and 148 are described. The patient was treated with chelation therapy during which she clinically improved considerably. A profound decrease in urinary mercury concentration occurred as well as normalization of the electroencephalogram.

Stevens-Johnson syndrome in a child with chronic mercury exposure and 2,3-dimercaptopropane-1-sulfonate (DMPS) therapy.

INTRODUCTION: Stevens-Johnson syndrome (SJS) is an uncommon and potentially serious mucocutaneous disease. The most important step in the management of SJS is early recognition and immediate withdrawal of the causative agent. We present a patient with SJS associated with dimercaptopropane-1-sulfonate (DMPS) therapy. CASE REPORT: An asymptomatic 11-year old boy who had been exposed chronically to mercury vapour had a 24-hour urine mercury concentration of 37 microgram/L (reference value <10 microgram/L). Exposure to the mercury vapour was stopped and treatment with oral DMPS was begun. After two weeks of therapy, he developed a disseminated cutaneous eruption of red pruritic macules on his chest and back, which three days later had spread all over his body with the discrete maculae becoming confluent; erosions and crusts developed on his lips and he had blisters in his mouth. The diagnosis of SJS was made, the DMPS was stopped, and the SJS resolved gradually. DISCUSSION: Chelation agents like DMPS or DMSA are increasingly used and are available over the counter in some countries. These drugs are used in patients with complaints that are attributed to mercury-containing dental amalgams and in children with autism. CONCLUSION: The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation. The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation.

Estimating biotransformation rate constants of organic chemicals from modeled and measured elimination rates.

In this study, biotransformation rate constants are estimated for a large set of organic compounds. Biotransformation (km) is considered part of the total elimination, further consisting of physico-chemical elimination to water (kw), depuration by feces (kf) and growth dilution (gamma). Existing models are used to estimate kw and kf, and gamma. The difference between measured elimination rate constants and the sum of predicted elimination rate constants for water, feces and growth indicates the ration of biotransformation in the total elimination. In all examined animal classes, polycyclic aromatic hydrocarbons seem to be metabolized at an intermediate rate. Because of the relative low hydrophobicity of some of the studied compounds, their physico-chemical elimination rate constant is relatively high, and the relative contribution of metabolism to total elimination of these compounds is therefore relatively low. Fish seem to be capable of metabolizing chlorodibenzo-p-dioxins and -furans, DDT, chloroanilines and phenol.

The power of size. 1. Rate constants and equilibrium ratios for accumulation of organic substances related to octanol-water partition ratio and species weight.

Most of the thousands of substances and species that risk assessment has to deal with are not investigated empirically because of financial, practical, and ethical constraints. To facilitate extrapolation, we have developed a model for accumulation kinetics of organic substances as a function of the octanol-water partition ratio (Kow) of the chemical and the weight, lipid content, and trophic level of the species. The ecological parameters were obtained from a previous review on allometric regressions. The chemical parameters, that is, resistances that substances encounter in water and lipid layers of organisms, were calibrated on 1,939 rate constants for absorption from water for assimilation from food and for elimination. Their ratio was validated on 37 laboratory bioconcentration and biomagnification regressions and on 2,700 field bioaccumulation data. The rate constant for absorption increased with the hydrophobicity of the substances with a Kow up to about 1,000 and then leveled off, decreasing with the weight of the species. About 39% of the variation was explained by the model, while deviations of more than a factor of 5 were noted for labile, large, and less hydrophobic molecules as well as for algae, mollusks, and arthropods. The efficiency for assimilation of contaminants from food was determined mainly by the food digestibility and thus by the trophic level of the species. A distinction was made between substances that are stable, that is, with a minimum elimination only, and those that are labile, that is, with an excess elimination probably largely due to biotransformation. The rate constant for minimum elimination decreased with the hydrophobicity of the substance and the weight of the species. About 70% of the variation was explained by the model, while deviations of more than a factor of 5 were noted for algae, terrestrial plants, and benthic animals. Labile substances were eliminated faster than isolipophilic stable compounds, but differences in laboratory elimination and accumulation were small compared with those in field accumulation. Excess elimination by vertebrates was faster than by invertebrates. Differences between terrestrial and aquatic species were attributed to water turnover rates, whereas differences between trophic levels were due to the food digestibility. Food web accumulation, expressed as organism-organic solids and organism-food concentrations ratios could be largely explained by ecological variables only. The model is believed to facilitate various types of scientific interpretation as well as environmental risk assessment.

Estimation of non-parametric multivariate risk functions in matched case-control studies with application to the assessment of interactions of risk factors in the study of cancer.

In epidemiological studies one is interested in investigating the probability of disease depending on risk factors and in particular in detecting interactions of risk factors. Within the setting of parametric logistic regression, interactions can be modelled only in a clumsy and limited way. Modelling the risk function non-parametrically, estimating it, for example, by a smoothing (thin plate) spline is attractive as a more explorative approach. For prospective studies this amounts to smoothing within the framework and distributional assumptions of generalized regression models (for binary observations). Case-control studies as retrospective studies with exposure to risk factors being observed do not immediately fit into this setting. In the special case of one-to-one matched studies, however, there is an appropriate likelihood again within the range of generalized models. Inferences will be illustrated using simulated and real data.

Norepinephrine release in the rat pineal gland: the input from the biological clock measured by in vivo microdialysis.

The sympathetic innervation of the rat pineal gland was investigated, measuring the norepinephrine (NE) release by on-line in vivo microdialysis. NE was assayed using an HPLC method with precolumn derivatization and fluorescence detection. Its high sensitivity and reliability made it very suitable to monitor the low levels of NE in the dialysates (12.5 fmol during nighttime, 3 fmol during daytime). To increase NE levels, the monoamine reuptake inhibitor cocaine was added to Ringer's solution at concentrations of 10(-6) and 10(-5) M. This resulted in increases of neurotransmitter output of 167 and 219%, respectively, but did not change the qualitative and/or quantitative outcome of other experiments. Perfusion with 10(-6) M tetrodotoxin for 1 h resulted in a decrease of the NE release by >80%, whereas perfusion with the alpha 2-receptor antagonist yohimbine caused a twofold increase. These results indicate that the NE release in the rat pineal was of neuronal origin and regulated by a negative feedback mechanism involving inhibitory presynaptic alpha 2-receptors. Long-term (i.e., 16 h) measurements are described, showing the circadian properties of NE release. A pronounced rhythm is reported, showing extremely sharp transitions between low daytime and high nighttime values. Increases and decreases are reported to occur within the duration of collecting one sample (20 min). For comparison, the rhythm of melatonin release was also recorded. The on and off switches of the sympathetic input correlated well with the circadian rhythm of melatonin release and can thus be considered as the primary clock signal, inducing the nightly production of melatonin.

Microdialysis reveals dynamics of coupling between noradrenaline release and melatonin secretion in conscious rats.

The coupling between noradrenergic innervation of the pineal gland and melatonin production was investigated. Previously, the development of a microdialysis technique was described which made it possible to study the noradrenaline (NA) input as well as the melatonin output with high time resolution. In the present study, we studied the effects of short-term changes in NA-release on melatonin secretion. A 1 min light pulse was applied around midnight and resulted in an immediate decrease of both NA and melatonin. While NA returned to basal levels in 40 min, melatonin did not reach the baseline within 2.5 h. This discrepancy in correlation between NA and melatonin indicates a rapid inactivation of N-acetyl-transferase (NAT), followed by a slow reactivation, possibly by de novo synthesis of NAT. During daytime, a perfusion with 60 mM potassium for 30 min, resulted in a rapid and short stimulation of NA release, which was not followed by an increase in melatonin production. This indicates that 30 min stimulation of NAT activation is not enough to increase the amount of melatonin produced. The combination of measuring NA input and melatonin output appears to be a valuable tool in studying the characteristics of pineal activity in great detail.

Spatial-temporal analysis of mortality using splines.

A method for constructing contour maps in disease mapping using smoothing splines is presented. Smoothing errors are discussed and error maps suggested. The approach is illustrated for mortality data on cardiovascular diseases in northwestern Germany (Lower Saxony and Bremen) 1970-1979.

Diagnostic and prognostic criteria for heat stroke with special reference to plasma enzyme and isoenzyme release patterns.

1. The aim of this study was to investigate the potential value of isoenzyme release patterns as parameters of hyperthermic injury in improving the diagnostic protocol for heat stroke. 2. Rats were exposed to combinations of exercise and hyperthermic stress. Following exposure, respective release patterns of isoenzymes were determined. 3. Isoenzyme release patterns following hyperthermic injury portray both the type and extent of tissue damage more clearly than do plasma total enzyme release patterns. 4. The sensitivity of isoenzymes as a diagnostic criterion is extended to include both a temporal component (i.e. an accurate diagnosis will be possible at an earlier stage subsequent to hyperthermic exposure) and at the same time to be indicative of the exposure.

Vitamin E deprivation in rats: some behavioral and histochemical observations.

Rats deprived of vitamin E from age of 4 weeks were tested in four independent behavioral experiments and compared with a group fed a control diet. During a 14-minute session in a hole-board, no differences in the level and the course of habituation of parameters of activity and exploration were found. A second group of animals was trained in an automatically controlled six-arm radial tunnel maze. Although no differences were found in various activity measurements, the deprived animals showed a slightly impaired spatial concept formation during 8 acquisition sessions. Testing their relearning ability of the same maze 18 days later, the vitamin E deprived animals showed a significant impairment. In a third experiment, animals were trained 16 days in the same maze configuration and at day 17 they were exposed to the mirror image of the radial maze. Both groups mastered this reversal with an increased level of activity but without differences in patrolling efficiency. In a fourth behavioral experiment, the effects of scopolamine on deprived animals were examined. Compared to the controls, the vitamin E deprived animals were relatively insensitive to the effects of scopolamine. Autofluorescent neuronal lipofuscin accumulation was found especially in the hippocampus (CA3) of vitamin E deprived animals. Based on these results, the usefulness of vitamin E deprivation as an animal model for accelerated normal aging is discussed.

Physiologic and biochemical changes during a triathlon competition.

The triathlon has come to be recognized as a distinct endurance event and although a substantial body of research information exists with regard to the individual components (canoeing, cycling, running, etc.), the physiologic demands imposed by combining the respective activities into one continuous event have not yet been assessed. Twenty-three male athletes (age = 33 +/- 5.2 yr; mass = 71.79 +/- 7.42 kg; height = 176.0 +/- 7.21 cm; means +/- SD) participated in the study on the basis of informed consent. Venous blood samples, taken immediately prior to and on completion of the Iron Man Triathlon held in Johannesburg during 1983, were assayed for parameters of energy metabolism, fluid and electrolyte balance, and stress (tissue enzymes in serum). On the basis of post-race blood glucose (6.17 mmol. l-1), free fatty acids (1943 mumol. l-1), and blood lactate (3.45 mmol. l-1) changes, it was concluded that the triathlon is primarily, in an overall sense, an aerobic event. With the exception of magnesium and iron, serum electrolyte changes agreed with literature findings. However, body mass reductions (average 3.23 kg, i.e., 4.5%) indicated that the extent of dehydration is more severe in the triathlon than in comparable endurance events. Post-race enzyme levels (LD, CK, and AST) were significantly elevated, and LD negatively correlated with total performance time (P less than 0.01). The general conclusion is that the physiologic demand of the triathlon exceeds that of other comparable endurance events.

Effect of beta-adrenoceptor blockade on thermoregulation during prolonged exercise.

The effect of clinically used equipotent doses of nonselective (beta 1/beta 2; propranolol) and selective (beta 1; atenolol) beta-adrenoceptor blockers on thermoregulation was studied during prolonged exercise in the heat. Oral propranolol (160 mg/day), atenolol (100 mg/day) or matching placebo were taken for 6 days each by 11 healthy young adult caucasian males. Subjects participated in 2 h of block-stepping at a work rate of 54 W in an environmental chamber with a temperature of 33.2 +/- 0.3 degree C dry bulb and 31.7 /+- 0.3 degree C wet bulb, 2 h after ingestion of the final dose of each drug. Both active agents produced similar marked (P less than 0.001) increases in subjective perception of effort, the mechanism of which was not immediately evident from changes in serum electrolytes, blood glucose, blood lactate, or ventilatory parameters. Propranolol did, however, cause a greater rise in serum K+ than placebo (P less than 0.02) and atenolol (P = NS) after exercise. Although rectal and mean skin temperatures were insignificantly altered by beta-adrenoceptor blockade, an increased total sweat production was noted with propranolol (P less than 0.01 vs. placebo) and to a lesser degree atenolol (P = NS vs. placebo) therapy. Analysis of the time course of sweat production showed the propranolol-mediated enhancement of sweating to ensue largely during the initial hour of block-stepping and to be transient in nature. The scientific and clinical implications of this observation will be dependent upon the precise underlying mechanism, a factor not identified by the present study.

A comparative study on the effect of training at altitude and at sea level on endurance and certain biochemical variables.

The aim of this study was to ascertain the effects of training at altitude (1750 m. PB = 630mmHg) and at sea level (10m, PB = 760mmHg) as well as that of a period of adaptation of originally sea level-trained rats at altitude on endurance capacity. The average run time to exhaustion was 185.3 +/- 3.7 min for rats trained at altitude in comparison with 150.0 +/- 10.3 min for sea level-trained rats. After 14 days of adaptation at altitude, no significant difference in running time to exhaustion between rats trained at altitude (189.0 +/- 16.4 min) and those trained at sea level (177.2 +/- 11.6 min) was apparent. The improved endurance capacity of rats trained at altitude (when tested at altitude) is probably attributable to an increased respiratory capacity as is evident from the significantly increased levels of the citric acid cycle marker enzyme, citrate synthase (citrate oxaloacetate-lyase, EC 4.1.3.7) in the liver and gastrocnemius muscle of rats trained at altitude as compared to those trained at sea level.