The LeVe CPAP System for Oxygen-Efficient CPAP Respiratory Support: Development and Pilot Evaluation.

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments. Technical Development + Testing: The LeVe ("Light") CPAP system was developed using principles of frugal innovation to produce a solution of low complexity and high resource efficiency. The LeVe system exploits the air flow dynamics of electric fan blowers which are inherently suited to delivery of positive pressure at appropriate flow rates for CPAP. Laboratory evaluation demonstrated that performance of the LeVe system was equivalent to other commercially available systems used to deliver CPAP, achieving a 10 cm H2O target pressure within 2.4% RMS error and 50-70% FiO2 dependent with 10 L/min oxygen from a commercial concentrator. Pilot Evaluation: The LeVe CPAP system was tested to evaluate safety and acceptability in a group of ten healthy volunteers at Mengo Hospital in Kampala, Uganda. The study demonstrated that the system can be used safely without inducing hypoxia or hypercapnia and that its use was well-tolerated by users, with no adverse events reported. Conclusions: To provide respiratory support for the high patient numbers associated with the COVID-19 pandemic, healthcare providers require resource efficient solutions. We have shown that this can be achieved through frugal engineering of a CPAP ventilation system, in a system which is safe for use and well-tolerated in healthy volunteers. This approach may also benefit other respiratory conditions which often go unaddressed in Low and Middle Income Countries (LMICs) for want of context-appropriate technology designed for the limited oxygen resources available.

An evaluation of an Internet-based approach to weight loss with low glycaemic load principles.

BACKGROUND: The prevalence of overweight and obesity is increasing worldwide at an alarming rate. An Internet-based weight-loss programme has the potential to reach larger numbers of people than traditional face-to-face programmes. A growing body of evidence supports the use of low glycaemic load (GL) diets for weight loss. The present study aimed to investigate the efficacy of an Internet-based weight-loss programme that included foods with a low GL. METHODS: One hundred and three volunteers, with a body mass index (BMI) ≥28 kg m(-2) , enrolled into an Internet weight-loss programme. A dietitian counselled participants over the Internet via weekly interactive chat rooms and monthly e-mails. Participants self-recorded body weight and food intake directly on to the Internet site. Weight, BMI and waist circumference were measured, and dietary data collected, at baseline and 6 months. RESULTS: Seventy participants completed the 6-month weight-loss programme. Among these, mean weight, BMI and waist circumference significantly decreased by 3.5 kg (95% CI = 2.3-4.7), 1.2 kg m(-2) (95% CI = 0.8-1.7) and 4.8 cm (95% CI = 2.8-6.8), of baseline values respectively (P < 0.001). Twenty-five (36%) of the 70 participants lost a clinically significant amount of weight (>5% of initial body weight). CONCLUSIONS: This descriptive study has shown that an Internet-based weight-loss programme with low GL principles can promote weight loss. This type of intervention and approach could be used to enhance other weight-loss strategies.

Review of wheat improvement for waterlogging tolerance in Australia and India: the importance of anaerobiosis and element toxicities associated with different soils.

BACKGROUND AND AIMS: The lack of knowledge about key traits in field environments is a major constraint to germplasm improvement and crop management because waterlogging-prone environments are highly diverse and complex, and the mechanisms of tolerance to waterlogging include a large range of traits. A model is proposed that waterlogging tolerance is a product of tolerance to anaerobiosis and high microelement concentrations. This is further evaluated with the aim of prioritizing traits required for waterlogging tolerance of wheat in the field. METHODS: Waterlogging tolerance mechanisms of wheat are evaluated in a range of diverse environments through a review of past research in Australia and India; this includes selected soils and plant data, including plant growth under waterlogged and drained conditions in different environments. Measurements focus on changes in redox potential and concentrations of diverse elements in soils and plants during waterlogging. KEY RESULTS: (a) Waterlogging tolerance of wheat in one location often does not relate to another, and (b) element toxicities are often a major constraint in waterlogged environments. Important element toxicities in different soils during waterlogging include Mn, Fe, Na, Al and B. This is the first time that Al and B toxicities have been indicated for wheat in waterlogged soils in India. These results support and extend the well-known interactions of salinity/Na and waterlogging/hypoxia tolerance. CONCLUSIONS: Diverse element toxicities (or deficiencies) that are exacerbated during waterlogging are proposed as a major reason why waterlogging tolerance at one site is often not replicated at another. Recommendations for germplasm improvement for waterlogging tolerance include use of inductively coupled plasma analyses of soils and plants.

High altitude may be synergistic with pulmonary hazards of appetite control medications fenfluramine and dexfenfluramine.

Clinical observations over the past 15 years incriminated first fenfluramine and recently dexfenfluramine in the provocation of primary pulmonary hypertension. Limited animal toxicology data tend to support this inference. The basis for respiratory pathology of high-altitude pulmonary malfunction, which reaches its maximal level in high-altitude pulmonary edema, evolves from and depends upon the occurrence of pulmonary hypertension. For this reason we hypothesize that high altitude and these two anorexic medications constitute a potentially synergistic combination, of which physicians treating patients for high-altitude illness, as well as those prescribing the drugs, should be aware.

Patient consent to observation. Responses to requests for written consent in an academic family practice unit.

OBJECTIVE: To examine patient rates of consent to observation and response to being asked for written consent. DESIGN: Patients were asked to provide written consent for a supervising physician to observe a resident performing a physical examination, or for both direct observation and videotaping of the visit. After the visit, all patients were interviewed, and patients who had given written consent completed a questionnaire. SETTING: The family practice unit at a teaching hospital affiliated with the University of Toronto. PARTICIPANTS: A representative sample of new and returning patients. MAIN OUTCOME MEASURES: Patient consent to observation or videotaping. RESULTS: Most patients (92.2%) agreed to be observed. Of those asked only for consent to observe, 97.3% agreed. Of those asked for consent to observe and videotape, 85.2% agreed. When specifically asked, 22% of patients who agreed to observation expressed concerns. CONCLUSION: We must devise clear policies and procedures for obtaining patient consent that are both sensitive to patients' concerns and administratively effective.

Additive hypothermic effects of cocaine and nicardipine in guinea-pigs.

1. This study investigated the thermoregulatory effects of cocaine combined with two reported antidotal treatments for acute cocaine overdosage, calcium channel blocker therapy and cold ambient temperatures. 2. Cocaine and nicardipine alone lowered the core temperature of female guinea-pigs (ambient temperature, 5 degrees C) which resulted in a drop in core temperature of approximately 2 degrees C at their highest respective doses (40 mg/kg and 50 mg/kg). 3. Nicardipine administration 30 min prior to cocaine caused an almost 2-fold drop in temperature (3.75 degrees C) relative to either drug alone. 4. The data suggest that cocaine and nicardipine produce hypothermia by different, but additive, mechanisms.

Genograms. Practical tools for family physicians.

A genogram can help a physician integrate a patient's family information into the medical problem-solving process for better patient care. A genogram allows a physician to obtain medical and psychosocial information from a patient easily and, as a result, to have a better understanding of the context of the presenting symptoms.

Effect of methyl methacrylate on isolated atria and interaction with isoproterenol, atropine and calcium chloride.

1. Spontaneous rate and contractile force of isolated rat and rabbit atria suspended in a tissue bath were recorded before and after drugs. Methyl methacrylate monomer (MMA) alone both decreased force and increased rate dose-dependently. 2. Concentrations of calcium chloride or isoproterenol that alone increased both rate and force of rat atrial contraction were fully and only partially able, respectively, to restore force to normal after MMA. 3. Atropine prevented changes in rat atrial function from low-effective doses of MMA, but not higher ones; it also failed to prevent the reduction of contractile force by a calcium channel blocker, verapamil. 4. There are similarities but also differences between actions of MMA and verapamil on rat atria.

Acute cardiovascular effects of methyl methacrylate monomer: characterization and modification by cholinergic blockade, adrenergic stimulation and calcium chloride infusion.

1. Methyl methacrylate monomer (MMA) given by i.v. infusion to anesthetized dogs caused a sustained hypotension, bradycardia, reduction of cardiac output and stroke volume, and increased peripheral resistance. 2. Epinephrine i.v. could reverse the hypotension but not the bradycardia; isoproterenol i.v. could reverse the bradycardia but not the hypotension. 3. Bilateral cervical vagotomy prevented bradycardia but not other cardiovascular effects of MMA, and prevented all respiratory effects except hypoxemia. 4. Calcium chloride i.v. reversed all circulatory changes except bradycardia; a combination of atropine and calcium reversed all cardiovascular changes from MMA.

Factors in the lethality of i.v. phencyclidine in conscious dogs.

1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP.

Effect of sex steroids on cocaine lethality in male and female mice.

1. Endogenous sex steroid levels were altered in mice via gonadectomy, via physiological or supraphysiological doses of testosterone and/or estradiol, and via tamoxifen dosing to antagonize estrogens. 2. The role of sex hormones in susceptibility to cocaine lethality was examined via the response of mice after endocrine alterations to an intraperitoneal (i.p.) cocaine HCl (75 mg/kg). Incidence of deaths was significantly decreased only in sham-operated males receiving estradiol or tamoxifen and in ovariectomized or sham-operated females receiving doses of estradiol. 3. The levels of estradiol in both sexes appeared to be more influential than were levels of testosterone as a determinant of susceptibility to cocaine.

Respiratory and circulatory effects of centrally administered phencyclidine in anesthetized dogs.

1. Anesthetized dogs were given phencyclidine HCl (PCP) by intracerebroventricular (i.c.v.) injection. 2. Physiological parameters were monitored after consecutive doses of 0.5, 1.0 and 2.0 mg of PCP. 3. Dose-related changes seen, including bradycardia, hypotension and bradypnea, were opposite to those produced by i.v. doses. 4. Single doses of 1.0 or 2.0 mg of PCP confirmed the prior observations, and the latter provided the baseline for further observations on dogs receiving PCP before various i.c.v. pretreatments--atropine, haloperidol, phentolamine or propranolol--in efforts to characterize the central neurotransmitter system(s) involved in the PCP effects.

2-Amino- and 2-guanidino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes as conformationally defined analogues of alpha-adrenergic agents.

The exo- and endo-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes++ + (3b and 4b, respectively) were prepared and evaluated as conformationally defined analogues of the alpha 1-agonist methoxamine. Only compound 3b exhibited significant alpha 1-agonist activity in the field stimulated rat vas deferens assay. Since 3b closely approximates the antiperiplanar form of (1R,2S)-(-)-erythro-methoxamine, the results suggest that methoxamine interacts with the alpha 1-adrenoceptor in the trans extended form. The exo-guanidino derivative 5 was found to be a partial alpha 1-agonist. Among the exo- and endo-2-amino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes (3a and 4a, respectively) prepared as rigid analogues of norephedrine, compound 3a possessed agonist activity at both alpha 1- and alpha 2-adrenoceptors, whereas 4a was inactive at either receptor.

Toxicity of MDA (3,4-methylenedioxyamphetamine) considered for relevance to hazards of MDMA (Ecstasy) abuse.

Despite a paucity of data on its animal pharmacology and toxicology, MDMA [Ecstasy, XTC, ADAM; (+/-)-3,4-methylenedioxymethamphetamine] was introduced as an "underground" (FDA-unapproved) adjunct to psychotherapy in the late 1970's and early 1980's, in addition to its use as a recreational drug. Analysis of the limited experimental literature indicates that LD50's for MDMA in five species by several routes of administration tend to predict a significant human toxicity. MDMA was either equally toxic or slightly to moderately less toxic than its close congener, MDA, (+/-)-3,4-methylenedioxyamphetamine. It is suggested that extrapolation of the pharmacologic/toxicologic data available for MDA to MDMA should be assumed to be valid until disproven. Recently published canine data describe physiologic disturbances caused by acute overdosage of MDA, and also indicate the utility of chlorpromazine as an antidote preventing fatalities associated with severe hyperthermia, lactacidemia, hypertension and tachycardia. The toxicology of MDMA warrants further direct study in view of its continuing illegal distribution.

Effects of anesthesia and phenoxybenzamine on responses of dogs to IV subtoxic doses of 3,4-methylenedioxyamphetamine (MDA).

Racemic 3,4-methylenedioxyamphetamine HCl (MDA) was tested for acute intravenous (i.v.) lethality in mongrel dogs. The LD50 and 95% confidence limits were 8.1 (7.0-9.4) mg/kg, and the LD1 and LD99 were approximately 5 and 14 mg/kg. Subtoxic doses (0.1, 0.3, 1.0 and 3.0 mg/kg, i.v.) were tested for acute effects on cardiovascular and respiratory functions in conscious dogs prepared surgically under local anesthesia and also in dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Four experimental groups were constituted, by pretreating or not, both conscious and anesthetized dogs with phenoxybenzamine HCl (15 mg/kg, i.v.). Arterial and left ventricular pressures tended to be elevated more by MDA in the anesthetized than in the conscious dogs. These and other cardiovascular parameters tended to be more fully antagonized by phenoxybenzamine in anesthetized than in conscious dogs. Respiratory rate was increased by higher doses, more so in the conscious group, but the increase was fully blocked by phenoxybenzamine. Possible clinical implications of the data are suggested.

Effects of an i.v. lethal dose of 3,4-methylenedioxyamphetamine (MDA) in the dog and antagonism by chlorpromazine.

A high intravenous (i.v.) dose of MDA (20 mg/kg) to mongrel dogs elevated body temperature, heart rate, mean arterial pressure and other cardiovascular parameters initially, but only the 1st two remained high. Other functions soon became quite depressed, and death shortly ensued. Arterial pO2 decreased, but pH and pCO2 showed a biphasic response after an initial decrease, Dogs that received chlorpromazine (10 mg/kg, i.v.) after MDA showed stabilization of physiological parameters, and survival through 48 hr.

A compact multichamber gas inhalation exposure system for mice.

A multi-unit, dynamic flow, inhalation exposure system which is capable of accommodating 12 mice per unit has been described. Components of the system include a mixing board, one or more glass distributing tubes, and detachable glass chamber tubes. The flow of a specified concentration of test gas exits from the mixing board, enters a distributing tube, and is then distributed equally to 12 chamber tubes housing one mouse each. Advantages includes quick equilibration time (10 min), relatively low flow rates (20 l/min per distributing tube), ease of disassembly for cleaning, compact size, modest expense and minimal temperature, pressure and physico-chemical effects.