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Biomedical subjects

D F Treacher

Publications and source records attributed to D F Treacher.

At least 37 records · Page 2Linked to original sources

Daily patterns of secretion of neurohypophysial hormones in man: effect of age.

The neurohypophysial hormone vasopressin contributes to control of urine output and, while urine flow shows a clear daily rhythm, there has been debate as to whether this is true of neurohypophysial hormones. A study was performed on fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood samples being taken at regular intervals for the determination of neurohypophysial hormones and indices of fluid balance. Samples were taken via an indwelling cannula so that sleep was undisturbed. A daily variation in the plasma concentrations of oxytocin and vasopressin was demonstrated with concentrations reaching a nadir in the late afternoon. Concentrations of both hormones peaked at 02.00 h. Vasopressin concentrations were inversely correlated with packed cell volume, indicating that the altered hormone release was affecting fluid retention. Consistent with this was the observation that the relationship of plasma osmolality to vasopressin depended on the time of day. To determine the effect of ageing, a similar study was performed on nine healthy elderly subjects with a mean age of 70 years. The nocturnal peak of vasopressin was markedly attenuated, while oxytocin release was similar to that in the younger group. These observations confirm the existence of a daily rhythm in the plasma concentrations of neurohypophysial hormones and indicate that the amplitude of the vasopressin change decreases with age.

Adult↗

A novel leucocyte-depleting filter for use in continuous venovenous haemofiltration: preliminary in vitro studies.

Multiple organ failure (MOF) secondary to circulatory shock, sepsis, or trauma was first described over 20 years ago. Despite much research effort and clinical trials of biological response modifiers, MOF continues to be the leading cause of death in both medical and surgical intensive care units (ICU). MOF is associated with widespread cellular and humoral systemic inflammatory responses which, in turn, are linked with inadequate tissue perfusion to vital organs and the inappropriate accumulation of activated neutrophils, resulting in microcirculatory injury. Much evidence suggests that such activated neutrophils cause vascular damage by adhering to the endothelium and releasing a variety of highly reactive and toxic moieties; these may subsequently produce endothelial injury and compromised organ function. We reasoned that a clinical device designed to remove such cells in a controlled fashion from the circulation of patients with MOF by means of using a continuous venovenous circuit might be beneficial. We report the leucocyte depletion performance of a novel filter medium as a first step towards the production of a clinical device, and show specific depletion of phagocytes relative to other formed elements in the blood.

Hemofiltration↗

Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation.

Increased delivery of aerosol to a model lung (attached to a mechanical ventilator) has been demonstrated with an ultrasonic nebulizer as compared to a jet nebulizer. This study examined whether the increased aerosol deposition with an ultrasonic nebulizer could also be demonstrated in vivo. Seven patients (6 male and 1 female) were studied during mechanical ventilalion (Siemens Servo 900C, Middlesex, UK) after open heart surgery. Two studies were performed in each patient. In the first study, aerosol was delivered via a Siemens Servo 945 nebulizer system (high setting) driving a System 22 Acorn jet nebulizer (Medic-Aid, Sussex, UK) containing 3 mL (99m)technetium-labelled human serum albumin (99mTc-HSA) (50 microg; activity 74 MBq). In the second study, a DP100 ultrasonic nebulizer (DP Medical, Meylan, France) containing 12 mL 99mTc-HSA (50 microg; activity 185 MBq) was used. Pulmonary deposition was quantified using a gamma camera. The humidification of the circuit and the ventilator settings were kept constant according to the patient's clinical requirements. The total lung aerosol deposition (mean+/-SD), as a percentage of initial nebulizer activity, was greater using the ultrasonic nebulizer than using the jet nebulizer (53+/-1.4 vs 2.3+/-0.9%; p<0.002). The ultrasonic nebulizer was also associated with a reduction in the time required to complete nebulization (9 vs 21 min, respectively) (p<0.0001). Use of the DP100 ultrasonic nebulizer more than doubled lung deposition compared with the System 22 jet nebulizers in mechanically-ventilated patients. Their efficiency, speed of drug delivery, and compatibility with mechanical ventilator circuits make ultrasonic nebulizers potentially attractive for use during mechanical ventilation.

Administration, Inhalation↗

Gastrointestinal permeability and absorptive capacity in sepsis.

OBJECTIVE: To assess gastrointestinal permeability and functional absorptive capacity in patients with sepsis. DESIGN: Case control study to analyze gastrointestinal permeability and functional absorptive capacity of septic patients by differential saccharide absorption (from an oral test solution) and excretion. SETTING: The intensive Therapy Unit of St. Thomas' Hospital, London, UK. PATIENTS: Twenty patients with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18.4 who were admitted to the intensive care unit with a diagnosis of sepsis. All patients were on enteral feeding. Patients with abdominal pathology were excluded. INTERVENTIONS: An oral test solution containing 5 g of lactulose, 1 g of L-rhamnose, 0.5 g of D-xylose, and 0.2 g of 3-O-methyl-D-glucose dissolved in water to a final volume of 100 mL was administered to patients and controls. Urine was collected for 5 hrs starting immediately after administration of the test solution and the saccharide content of the urine was estimated and expressed as a percentage recovery of the oral test solution. MEASUREMENTS AND MAIN RESULTS: Septic patients had increased lactulose/L-rhamnose urine excretion ratios (0.23 +/- 0.19) compared with control subjects (0.03 +/- 0.01, p < .001), consistent with increased gastrointestinal permeability in sepsis. Septic patients had decreased L-rhamnose/3-O-methyl-D-glucose urine excretion ratios (0.14 +/- 0.07) compared with normal controls (0.28 +/- 0.08, p < .001), consistent with decreased gastrointestinal functional absorptive capacity in sepsis. CONCLUSIONS: Patients with acute sepsis exhibit increased gastrointestinal permeability and decreased gastrointestinal functional absorptive capacity in comparison with healthy control subjects. These abnormalities may contribute to the pathophysiology of sepsis.

3-O-Methylglucose↗

Clinical aspects of hypoxic pulmonary vasoconstriction.

Although frequently unrecognized, hypoxic pulmonary vascular disease is an important cofactor in the morbidity and mortality of a wide spectrum of disease processes. The hypoxic response incorporates two distinct phases, the acute hypoxic vasoconstrictor response and vascular remodelling associated with prolonged alveolar hypoxia. Understanding of the mechanisms causing both processes has increased rapidly and may result in the near future in specific treatment aimed at correcting underlying physiological abnormalities. However, currently available therapies remain limited to correction of the hypoxaemia and generalized non-specific pulmonary vasodilatation. The recent development of inhaled NO therapy represents a significant advance in the management of the acute hypoxic pulmonary vasoconstriction occurring during critical illness.

Animals↗

Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation.

BACKGROUND: Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition of a spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo. METHODS: Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labelled human serum albumin (99mTc-HSA (50 micrograms); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple T-piece or a 600 ml spacer. RESULTS: The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2.2 (0.7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18.2 min v 18.3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46.2% v 47.1% respectively). CONCLUSIONS: The combination of a spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation.

Aerosols↗

Critical illness poly-neuropathy following severe hyperpyrexia.

Two patients developed critical illness polyneuropathy after severe hyperpyrexia. Fever was secondary to a phaeochromocytoma in one patient and sepsis in the other. These observations suggest that high fever may be one possible aetiology of critical illness polyneuropathy.

Adrenal Gland Neoplasms↗

Effects of a patent foramen ovale on arterial saturation during exercise and on cardiovascular responses to deep breathing, Valsalva manoeuvre, and passive tilt: relation to history of decompression illness in divers.

OBJECTIVE: To determine whether the presence of a patent foramen ovale could result in significant arterial desaturation and affect the responses of heart rate and blood pressure to physiological manoeuvres and to determine whether responses differed between those with and those without prior clinical events associated with a patent foramen ovale. DESIGN: Blind controlled study. SETTING: Teaching hospital. PATIENTS: Divers with a large patent foramen ovale shown by contrast echocardiography and divided into those who had neurological decompression illness that started within 30 minutes of surfacing (group 1), those who had no history of decompression illness (group 2), and age and sex matched control divers who had no evidence of intracardiac shunts (group 3). MAIN OUTCOME MEASURES: The change in percentage haemoglobin oxygen saturation during treadmill exercise and the response of heart rate and blood pressure to physiological manoeuvres. RESULTS: There were no significant differences between the three groups but two divers in group 1 showed clinically important desaturation during exercise and unusual blood pressure and heart rate responses to passive tilt. These divers were notable for having the greatest number of episodes and the most severe single episode of spinal cord decompression illness. CONCLUSION: A large patent foramen ovale may be associated with clinically significant arterial desaturation and unusual responses of heart rate and blood pressure in some healthy subjects.

Arteries↗

The relationship between oxygen delivery and consumption.

The primary function of the heart and lungs is to generate a flow of oxygenated blood to respiring tissues to sustain aerobic metabolism. Teleologically, such a transport system has several basic requirements. It should be energy efficient, avoiding unnecessary cardiorespiratory work, but it should be sensitive to the fluctuating demands of cellular metabolism. Ideally, metabolic demand and oxygen distribution should be matched regionally when at rest, during exercise, and in different disease states. Finally, oxygen should pass efficiently across the extravascular tissue matrix. The mechanisms that control oxygen distribution are complex and not completely understood. In the critically ill patient, these mechanisms may have an important role in determining the clinical outcome. The relationship between oxygen delivery and consumption has not been clearly established despite considerable investigation during the last decade. However, these variables are often measured to define a population of critically ill patients in whom oxygen consumption is limited by oxygen delivery, the state of so-called delivery-dependent oxygen consumption or pathologic supply dependency. The recent literature in critical care and many leading intensive care units has emphasized the importance of raising oxygen delivery to "supranormal" levels in an attempt to satisfy the increased metabolic demands of these patients. This practice has been justified by the observation that increasing oxygen delivery improves oxygen debt and outcome in postoperative surgical patients requiring intensive care. In the severely hypovolemic patient, most physicians would agree that volume replacement to improve oxygen delivery must be beneficial. However, in patients with more complex problems, including sepsis, cardiovascular collapse, and hypoxic hypoxemia, controlled trials to examine the influence of such strategies on clinical outcome have produced conflicting data. Several methodologic factors may have contributed to these contradictory and often controversial results. These factors include failure to define the disease and patient population adequately, the relationship between the time of investigation and the evolution of the disease process, and the accuracy and frequency of measurement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pulmonary deposition of a nebulised aerosol during mechanical ventilation.

BACKGROUND: There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. METHODS: Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. RESULTS: Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). CONCLUSIONS: Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients.

Administration, Inhalation↗

Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation.

Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted.

Adult↗

Venesection in haemoglobin Yakima, a high oxygen affinity haemoglobin.

High oxygen affinity haemoglobins result in polycythaemia and cardiovascular adaptation to maintain tissue oxygenation. The polycythaemia can cause symptoms of hyperviscosity and vaso-occlusive disease. We report a kindred with a high affinity haemoglobin (Haemoglobin Yakima) one of whose members gave birth to two infants with intra-uterine growth retardation and who suffered with symptoms of hyperviscosity which settled on reduction of the PCV by venesection.

Adolescent↗

The haemodynamic responses to venesection and the effects of cardiovascular disease.

The haemodynamic effects of the venesection of one unit (450 ml) of blood over 9 min were measured using non-invasive techniques, in 14 healthy controls and 18 patients with coronary heart disease or hypertension. Venesection was associated with significant reductions in supine and standing systolic and diastolic blood pressure, stroke volume index and cardiac index, and increases in standing heart rate, in both patient groups. No significant differences were observed between the responses of subjects with and without cardiovascular disease. The authors conclude that, in contrast to established teaching, blood loss can be detected in its early stages by careful haemodynamic monitoring and that venesection can be performed safely without volume replacement in patients with stable cardiovascular disease.

Adult↗