Physician payment reforms and family physicians.
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Biomedical subjects
Publications and source records attributed to J G Jones.
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1. General anaesthesia is a state of analgesia and impaired cognitive function that results from the depressant effects of anaesthetics. 2. Graded increases in anaesthetic concentration cause a progressive impairment of cognitive function, the extremes of which are commonly described as "light" and "deep" anaesthesia. 3. Surgical stimulation produces activation in the EEG and may arouse a patient from a deeper to a lighter state of cognitive function. 4. It may be very difficult, particularly in patients with neuromuscular blockade, to identify a change in state which results in conscious awareness. 5. A range of methods has been used for evaluating depth of anaesthesia. 6. The evidence reviewed in this paper suggests that the median frequency in the EEG and the auditory evoked potential appear to be the best techniques for monitoring the graded effects of anaesthetics on the brain. 7. The median frequency, which is 10 Hz in conscious subjects, should be kept below 5 Hz during anaesthesia to ensure that there is no response to verbal command. 8. The auditory evoked potential measures the resulting effects of anaesthetic depression and surgical stimulation which is "depth of anaesthesia". 9. However it is not yet certain whether a particular feature e.g. Nb latency, or a collection of features between 20 and 80 msec gives the most reliable index of conscious awareness.
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We have examined in vitro the antioxidant properties of 2,6-diisopropylphenol. In studies using electron spin resonance spectroscopy we have demonstrated that 2,6-diisopropylphenol acts as an antioxidant by reacting with free radicals to form a phenoxyl radical--a property common to all phenol-based free radical scavengers. In additional experiments, the antioxidant properties of the clinical formulation of 2,6-diisopropylphenol (propofol) have been measured using an assay of antioxidant potential. In these experiments, propofol, but not Intralipid, was found to exhibit significant antioxidant activity, such that in the range of propofol concentrations examined (10(-6)-10(-5) mol litre-1), each molecule of 2,6-diisopropylphenol was able to scavenge two radical species. We conclude that the free radical scavenging properties of 2,6-diisopropylphenol resemble those of the endogenous antioxidant alpha-tocopherol (vitamin E).
A new technique for recording and analysing continuous measurements of oxygen saturation (SpO2) by pulse oximeter during haemodialysis was used to compare changes in SpO2 in eight patients during two 4 h periods of dialysis using a cuprophane membrane, once using an acetate dialysate, and once using bicarbonate. The computer-derived patterns of SpO2 show whether hypoxaemia was caused mainly by extrapulmonary abnormalities (ventilatory control) or intrapulmonary abnormalities (V/Q distribution). The patterns of oxygen saturation were analysed for (i) stability, (ii) the lower median 20th centile of SpO2, and (iii) time below a SpO2 of 90%. Not all patients had reduced oxygenation during acetate dialysis. Three of eight patients had a stable pattern with acetate dialysis and six of eight were stable with bicarbonate. Five of eight patients had a lower SpO2 with acetate but one patient had a lower SpO2 with bicarbonate. Four patients had prolonged, clinically significant periods of oxygen desaturation with SpO2 less than 90%; two of these had particularly prolonged periods during acetate (62 min and 12 min), but one patient showed a longer period during bicarbonate than acetate dialysis (7 min). In two patients the SpO2 declined to less than 84%. The patterns of SpO2 suggested that the decrease in oxygen saturation was due more to extrapulmonary abnormalities causing an instability in ventilatory control rather than to venous admixture. It is recommended that pulse oximetry is used to identify patients at risk of hypoxaemia, to monitor these patients during haemodialysis, and to administer oxygen to those whose SpO2 falls below 90%, particularly if they have anaemia or cardiovascular disease.
Although intralesional corticosteroid injection of subcutaneous rheumatoid nodules was mentioned in 1968, this simple procedure is not commonly practised. A placebo-controlled, double-blind trial of intralesional corticosteroid injection using 24 rheumatoid nodules from 11 patients was carried out to determine the efficacy and safety of the procedure. Nodules injected with methylprednisolone and lignocaine regressed significantly more than nodules injected with placebo (lignocaine alone). This was consistently shown in all modalities of assessments which included patients' assessments (P < 0.001) and investigator's assessments (P < 0.001) of the percentage change in nodule size, and gross measurements of nodule volumes using a pincer (P < 0.001). Nine of 12 active injections produced > or = 50% loss in nodular volume with complete disappearance of two nodules. This compares with only one out of 12 placebo injections which resulted in > or = 50% loss in nodular volume. The patients found all 12 active injections to be worthwhile compared to only two of 12 placebo injections being worthwhile. The only complication of injection therapy observed was that of pain during the procedure.
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In present practice, patients in intensive care are managed with subnormal haematocrit values and oligovolaemia. Optimization of the blood for oxygen transport in preterm infants in intensive care yields major benefits in their prognosis. A rational basis is described for this optimization in terms of the circulating blood volume and haematocrit, represented by circulating red cell volume (mass). Extrapolation of these lessons in haematological management is proposed for adult patients in critical care, so as to reduce dependence on respiratory support and minimize clinical complications and costs.
The metabolism of methanol was monitored in whole cells of the methylotrophic yeast Hansenula polymorpha by using [13C]methanol and n.m.r. in vivo. The main products observed under normal conditions were trehalose and glycerol, whereas cells that were starved before exposure to [13C]methanol also accumulated glutamate, glutamine and alanine; formate was also more prominent in spectra from starved cells. Cells exposed to high methanol concentration together with high oxygenation oxidized methanol extensively, leading to formaldehyde accumulation; label was not found in any subsequent metabolic products, indicating possible cell inactivation. [13C]Formate was incorporated into metabolic products in glucose-grown cells exposed to 150 mM-methanol for 3 h, but not in cells starved for 3 h, in which it was oxidized. At 21 degrees C such 3 h-starved cells showed a slower metabolism of [13C]methanol compared with those at 37 degrees C, and also converted methanol into formate rather than into assimilation products. The labelling pattern in trehalose from starved cells at 37 degrees C was consistent with methanol assimilation via the pentose phosphate pathway. Lack of appearance of labelled formaldehyde and formate during metabolism under normal conditions suggests that the linear oxidation pathway is not a major contributor to methanol oxidation; their appearance in extreme conditions suggests instead a more likely role in detoxification.
Pseudomonas species MA was grown with methylamine as a sole source of carbon and nitrogen enabling the total flow of carbon and nitrogen into this organism to be simultaneously monitored in vivo using 13C and 15N NMR. [13C]Methylamine was rapidly and extensively incorporated into the methyl group of N-methylglutamate during high oxygenation of the cell suspension, but when the oxygenation rate was lower, a significant portion was also found in the methyl group of gamma-glutamylmethylamide. At later times the carbon label was found in intermediates of the serine assimilation pathway, with glutamate derived from the tricarboxylic acid cycle being the most abundant product. Incorporation of [15N]methylamine was only detected as N-methyl[15N]glutamate, but when protein synthesis was inhibited, the label was also detected in the amino nitrogen of glutamate. When oxygenation rates were lower, the 15N-labeled methylamine was found in the methylamide group of gamma-glutamylmethylamide in addition to being incorporated into N-methylglutamate. gamma-Glutamylmethylamide formation was linked to the overall energy state of the cell and was not affected by inhibition of the carbon assimilation pathway. Neither 5-hydroxy-N-methylpyroglutamate nor N-methyl-alpha-ketoglutaramate were detected to any significant extent. A mechanism was proposed for the role of gamma-glutamylmethylamide in the regulation of endogenous nitrogen supplies in this organism.
Halobacterium halobium strain NRC-1 contains intracellular gas-filled vesicles (GVs) that confer buoyancy to the cells. Cloning of the major GV protein (GvpA)-encoding gene, gvpA, and analysis of GV-deficient mutants (Vac-) of H. halobium led to the identification of a region of a 200-kb plasmid, pNRC100, important for GV synthesis. We report here the nucleotide sequence of an 8520-bp region which, including gvpA, contains twelve open reading frames (ORFs) that are organized into two divergent transcription units, gvpAC oriented rightward, and gvpD, E, F, G, H, I, J, K, L, and M located upstream from gvpAC and oriented leftward. Insertions into the gvpA promoter and gvpD and E resulted in the Vac- phenotype. The overall gene organization is highly compact with the end of one ORF overlapping with the beginning of the next in most cases. The gene cluster is bracketed by two ISH8 element copies in inverted orientation, an organization suggestive of a composite transposon. Comparison of predicted amino acid sequences showed homology between GvpA, and the gvpJ and gvpM putative gene products. The putative gvpC gene product contains eight copies of an imperfectly repeated sequence with similarity to repeats in a cyanobacterial GvpC plus a highly acidic C-terminal region not found in the cyanobacterial homologue.
We examined the effect of a clinically detectable patent ductus arteriosus (PDA) and its successful treatment with indomethacin on serial measures of pulmonary mechanics in 10 very-low-birthweight (VLBW) intubated infants with respiratory distress syndrome (RDS). Pulmonary mechanics were measured by the passive expiratory flow technique. Total respiratory system compliance (Crs) gradually improved as RDS resolved. However, a significant decrease in mean Crs was associated with the development of a clinically detectable PDA, ranging from 1.51 +/- 0.21 to 0.90 +/- 0.08 mL/cmH2O/m (P less than 0.05). We also noted an increase in mean Crs, from 0.90 +/- 0.08 to 1.49 +/- 0.21 mL/cmH2O/m (P less than 0.05), after successful treatment of a PDA with indomethacin. Total respiratory system resistance (Rrs) did not change. We conclude that a clinically significant PDA is associated with a decreased Crs and that successful treatment of a PDA with indomethacin is associated with an improvement in lung compliance. These findings imply that the development of a clinically detectable PDA and its subsequent treatment complicates the interpretation of pulmonary mechanics data in VLBW infants with RDS.
Metastasis is a multistep process in which amoeboid chemotaxis plays a key role in the movement of tumor cells into and out of vessels. On a molecular level, much of what is known about amoeboid chemotaxis has been learned through work with Dictyostelium discoideum, a lower eukaryotic amoeboid phagocyte. One of the first and most crucial events to occur in the actin cytoskeleton following chemotactic stimulation is activation of actin nucleation. This is followed by incorporation of specific actin cross-linking proteins into the cytoskeleton, proteins which are implicated in the extension of pseudopods and filopods. Together, these events have been termed the Cortical Expansion Model for amoeboid chemotaxis. Detailed biochemical analysis has implicated a new actin-capping protein and has shown that one of the cross-linking proteins is Elongation Factor 1a, suggesting a link between chemotaxis and growth control. Preliminary data from parallel studies on neoplastic cells are presented.
Neuroendocrine cell carcinoma of the cervix is a virulent tumor associated with an extremely poor prognosis. Even in clinical Stage I disease, there may be subclinical hematogenous and lymphatic metastases with frequent recurrences. Adjuvant postoperative external pelvic radiotherapy has been reported to offer some degree of local control; however, most patients succumb to distant disease. Following radical abdominal hysterectomy and pelvic lymphadenectomy, with confirmation of the neuroendocrine tumor by electron microscopy and immunohistochemical staining, two patients were given adjuvant systemic chemotherapy with concurrent pelvic radiotherapy, employing regimens with documented activity against small cell carcinoma of the lung of neuroendocrine origin. Despite severe myelotoxicity and persistent neuropathy, both patients are alive without clinical evidence of disease at 28+ and 47+ months.
The study aimed to determine the base/restoration combination which allowed the least microleakage in Class II cavities. One hundred premolar teeth were prepared with a standardized, minimal two-surface cavity and randomly ascribed to ten equal groups. The cavities were restored by use of one of ten different material/technique combinations. Restored teeth were sealed to within 1 mm of the restoration margins with nail varnish prior to the immersion of the crowns in 5% (buffered) eosin for 48 h. The teeth were then hemisected longitudinally, in a mesio-distal plane, through the midline of the restoration by means of a diamond disc with water coolant, and one half of each tooth was then photographed. The transparencies were examined by image analysis programmed to facilitate calculation of the percentage of the tooth/restoration interface and of the crown dentin exhibiting dye penetration. Light- and chemically-cured glass-ionomer-based restorations showed similar amounts of leakage when expressed as a percentage area of crown dentin. This was significantly (p less than 0.05) less than that shown by cavities both etched and bonded. Cavities restored without enamel etching or involving the use of a bonding system exhibited significantly (p less than 0.05) greatest leakage.
The clinical features of GCA can be classified into: (1) the systemic manifestations of malaise, weight loss, fever, night sweats and depression; (2) the proximal muscle pain and stiffness of polymyalgia rheumatica; (3) arteritic manifestations of pain or tenderness due to local inflammation; and (4) arteritic manifestations of ischaemia due to narrowing or occlusion of vessels. These may occur singly or in any combination and may come and go with the passage of time. Thus GCA can result in many different clinical signs and symptoms. The feared ocular and cerebrovascular complications of the condition can be prevented by the early institution of corticosteroid treatment. Early diagnosis is therefore vital. This is a simple matter when GCA presents in the classical textbook manner, but in atypical cases diagnosis can be exceedingly difficult. The absence of a reliable way of excluding the disease means that diagnosis is often a clinical exercise. A sound knowledge of the many and varied clinical manifestations of GCA is therefore required if the physician is going to prevent the ocular and cerebrovascular complications of GCA by early diagnosis and treatment.
In order to gain an understanding of the physiological stresses imposed by the wearing of a single-use disposable respirator, a series of experiments was done to measure the cardiopulmonary effects of wearing the respirator (heart rate, respiratory rate, and blood pressure); resistance to breathing while wearing a respirator; and heat stress imposed by the use of a respirator (changes in inspired and expired air temperature). Ten men, ages 24 to 35, of varying fitness levels, served as volunteers in the studies. All the men exercised on a treadmill both with and without 3M Model 8715 disposable respirators. Workloads corresponding to light, moderate, and heavy levels were calculated for each volunteer based on his maximal oxygen uptake. As work intensity increased, an increase in breathing resistance was found. Peak resistances were in the range of +/- 2 cm water. Work-intensity level increases in respiratory rates were found with and without the respirators, but the respirator use trial had a significantly increased respiratory rate. Heart rate also showed a dose-related increase as work intensity increased and was significantly greater in the respirator trials at heavy levels of work and during recovery. Systolic blood pressure showed a biphasic response to respirator use, being significantly lower at rest and higher at high levels of work. Diastolic blood pressure changes were less dramatic but were elevated in the respirator trials. Clinically important increases in blood pressure were found in two volunteers when respirators were worn. Air temperatures immediately anterior to the face were, on average, 7.5 degrees C higher in the respirator trials.(ABSTRACT TRUNCATED AT 250 WORDS)