Comparison of a modified microagglutination technique for HBsAg with the standard technique and a new RIA system.

A further modification of the standard RPHA technique (Hepatest, Wellcome Reagents) for the detection of HBsAg is described. This modification does not require a centrifugation step which is required by the other modifications that have been described previously and consequently takes a little longer to perform. It does, however, retain the advantages of increased sensitivity and decreased costs which are also features of the other modifications. A series of 939 routine clinical specimens were used to evaluate the method described and to evaluate a new RIA kit for the detection of HBsAg (Hepatube, Wellcome Reagents). Of 53 specimens found to be positive for HBsAg by RIA, 50 (94% were detected by the modified Hepatest RPHA as opposed to 47 (89%) by the standard technique.

Pressure-limited ventilation with permissive hypercapnia and minimum PEEP in saline-lavaged rabbits allows progressive improvement in oxygenation, but does not avoid ventilator-induced lung injury.

OBJECTIVE: To determine whether pressure-limited intermittent mandatory ventilation with permissive hypercapnia and positive end-expiratory pressure (PEEP) titrated to arterial oxygen tension (PaO2) prevents or reduces acute lung injury, compared to conventional ventilation, in saline-lavaged rabbits. DESIGN: Prospective randomised trial. SETTING: University animal laboratory. SUBJECTS: 18 New Zealand White rabbits. INTERVENTIONS: Following five sequential saline lung lavages, anaesthetised rabbits were randomly allocated in pairs to receive either of two ventilation protocols using intermittent mandatory ventilation. The study group had peak inspiratory pressure limited to 15 cm H2O and arterial partial pressure of carbon dioxide (PaCO2) was allowed to rise. The control group received 12 ml/kg tidal volume with rate adjusted for normocarbia. PEEP and fractional inspired oxygen (FIO2) were adjusted to maintain, PaO2 between 8 and 13.3 kPa (60 and 100 mm Hg) using a predetermined protocol. At 10 h or following death, lung lavage was repeated and lung histology evaluated. MEASUREMENTS AND MAIN RESULTS: The mean increase in lavage cell counts and protein concentration and hyaline membrane scores were not significantly different between the groups. Oxygenation progressively improved more in the study group (p = 0.01 vs control for PaO2/FIO2 ratio and alveolar-arterial oxygen tension gradient (AaDO2)). PEEP was similar and the mean airway pressure higher in the control group, suggesting that this probably resulted from less ventilator-induced injury in the study group. Four deaths occurred in the control group (three due to pneumothorax and one to hypoxaemia) and none in the study group (p = 0.08). CONCLUSIONS: This ventilatory protocol may have failed to prevent lung overdistension or it may have provided insufficient PEEP to prevent injury in this model; PEEP greater than the lower inflection point of the pressure-volume curve has been shown to prevent injury almost entirely.

Chlorinated hydrocarbons in the tissues of South Polar Skuas (Catharacta maccormicki) and Adélie Penguins (Pygoscelis adeliea) from Ross Sea, Antarctica.

High rates of egg infertility and embryo death in a colony of South Polar Skuas breeding in the Antarctic were similar to those in polluted North Atlantic populations of the Great Skua. Such loss could not be linked to factors such as organochlorine pollutants, as levels of DDE and PCBs in the contents of skua eggs from the population were only a small fraction of those in polluted skua populations from the Northern Hemisphere. Average eggshell thickness for skuas nesting on Ross Island has shown no significant change since the introduction of DDT. Concentrations of DDE and PCBs in South Polar Skuas were 13 and 22 times higher, respectively, than those in the eggs of sympatric Adélie Penguins, and this probably reflects the greater exposure of skuas to pollution when they migrate north of the Antarctic Convergence in winter. Residues in liver tissue showed a similar trend, and a higher rate of mixed function oxidase induction in skua liver compared to that of penguins is consistent with the trends seen in pollutant levels. The same PCB congener predominated in both skua and penguin samples. Comparisons with historical residue data suggest that global levels of DDT residues are declining.

Long-term trends and sources of organochlorine contamination in Canadian tundra Peregrine Falcons, Falco peregrinus tundrius.

Levels of eggshell thinning, and organochlorine residues in egg contents, blood plasma of adults and juveniles, tissue samples, and prey species were determined for a population of migratory Peregrine Falcons (Falco peregrinus tundrius) breeding in the Canadian Arctic. Temporal trends were assessed by comparing data collected during 1991-1994, with data from 1982-1986, for the same population. Shells (n=54) from 1991-1994 averaged 15% thinner than eggs produced prior to the introduction of DDT. No improvement in shell thickness was detected between decades. Mean DDE residue levels in eggs showed a decline from 7.6 mg kg (1982-1986) to 4.5 mg kg (1991-1994), but there was no significant change in SigmaPCB residues. Moreover, the proportion of clutches with eggs exceeding critical SigmaPCB, DDE, and dieldrin residue levels (10%) did not change between decades. Relative to Greenland and Alaskan populations, F. p. tundrius at Rankin Inlet show high levels of organochlorine contamination and little reduction in residues over the last decade. These Tundra Peregrines continue to be exposed to organochlorines in Latin America; however, results also link relatively high levels in the study population with waterfowl species that do not leave Canada in winter.

Ideal endotracheal tube placement by referencing measurements on the tube.

The ideal position of the endotracheal tube (ETT) within the trachea is 5 +/- 2 cm from the carina with the head and neck in neutral position (Goodman's criteria). We assessed the possibility of achieving ideal placement of ETTs in our population by positioning them at reference marks of 23 cm in men and 21 cm in women. From January 1995 to April 1995, 105 intubated patients in the Medical Intensive Care Unit, Singapore General Hospital were studied. The mean distance of the ETT tip from the carina was 4.02 cm +/- 3.90. The ETT tip was < 3 cm from the carina in 30 cases (28.6%) with one case resulting in endobronchial intubation. These 30 patients were significantly shorter in height when compared to the rest of the study population (P = 0.01). Five cases (4.8%) had ETT tip > 7 cm from the carina. Adopting the above-mentioned reference marks did not result in ideal positioning of ETTs in a significant proportion of cases (33.4%). We postulate that this is because our Asian population is generally shorter than those in previous studies which had achieved ideal ETT positioning using similar reference marks.

Noninvasive positive-pressure ventilation for acute respiratory failure in a medical intensive care unit in Singapore.

The main advantage of noninvasive ventilation over conventional mechanical ventilation is in the avoidance of endotracheal intubation and its related complications. Currently, the role of noninvasive ventilation in the management of patients with acute respiratory failure is still not firmly established. We conducted a prospective study to evaluate the efficacy of nasal positive pressure ventilation in patients with acute respiratory failure. Thirty-three consecutive patients with acute failure in whom intubation and mechanical ventilation were strongly considered were included in the study. They received ventilatory support by means of BiPAP ventilatory support system and nasal mask. Physical findings and laboratory measurements were documented before and at specific intervals after initiation of support. Eighty per cent (24/30) of patients were successfully supported. Successfully supported patients tolerated the device with improved gas exchange, hence avoiding endotracheal intubation. The mean duration of support was 19.2 hours. There were major associated complications, e.g. gastric distention or aspiration.

The production of antibodies for radioimmunoassay.

Three factors which affect the outcome of any immunisation schedule designed to produce antisera for radio-immunoassay, the antigen, the method of immunisation and the choice of animal are considered. Several factors concerning the nature of the antigen are dealt with, for example, the molecular size and immunogenicity of the antigen. It is noted that the larger polypeptide and proteins are sufficiently immunogenic to elicit a useful antibody response alone and that whilst substances with molecular weights of less than 2000 may produce a response alone they will probably produce a better one if they are conjugated (chemically coupled) to a much larger molecule. With the low molecular weight substances such as the thyroxine, steroid hormones, and drugs which are of much clinical interest to many people conjugation is essential. The availability and purity of the immunogen are considered, especially in cases where a minute amount of material has been produced following a long and tedious purification procedure. The necessity in such instances that workers are aware of the smallest amount of material that will produce a useful antibody response and also of the most effective method of immunisation is stressed. The method of immunisation is discussed including a consideration of the use of adjuvant and the route and timing of injections. It is noted that antisera showing the relevant properties for radio-immunoassay are rarely produced without emulsification of the immunogen in Freund's adjuvant although this is not an absolute requirement for antibody production. Data are presented comparing the intramuscular and multiple intradermal routes of injection. The results, however, fail to demonstrate any major advantage for either method although the latter may be more economical, producing high titre antisera with relatively small amounts of immunogen. Because of their convenience rabbits are generally the first choice of animal for raising antisera for radioimmunoassay although guinea pigs, chickens and sheep have been used successfully in many cases.

High service users: does the clinical psychologist have a role?

OBJECTIVE: To assess the impact of psychological intervention on high users of the GP service. DESIGN: A sample of high-attenders was offered the opportunity to attend an interview with a clinical psychologist. A three-year (one year before and two years after psychological intervention) survey of patient records was carried out to determine the pattern of patient attendances. In addition, GP and patient satisfaction questionnaires were utilised to rate the psychological service. SETTING: A GP surgery situated in the coastal region of Scotland. SUBJECTS: All adult patients, who had consulted over 12 times in the 12 months prior to the beginning of the study except those who had ongoing medical problems that the GP felt were being dealt with adequately, were invited to a psychological interview. In all, 174 invitations were sent, and 101 agreed to psychological intervention. RESULTS: After three months both the GPs and patients positively rated the input of the psychologist. There were short-term benefits from the psychological intervention in terms of attendance rates, which were not in evidence in the long term. For the participating group there was a significant decrease in attendance rate three months after psychological intervention compared to the non-participating group (P < 0.001). However, at 12 and 24 months after intervention both groups reduced attendance at a similar rate. CONCLUSION: Psychologist intervention had a short, but not long term, benefit, in reducing attendance rates. However, both GPs and patients found the provision of a report from the psychologist useful.

Large scale screening programme for selection of antisera for radioimmunoassay of human parathyroid hormone.

A large-scale, three-phase screening programme has been devised for the rapid selection of antisera which might be of potential use in clinical radioimmunoassays for human parathyroid hormone. A total of 122 sera from 169 guinea pigs and 6 rabbits immunized with bovine parathyroid hormone, and 12 guinea pigs immunized with human parathyroid hormone were assessed relative to reference antisera. Pre-determined criteria for the three phase programme were imposed by the requirement for antisera that could be used at dilutions greater than 10(-5) in order to ensure continuity of supplies for wide-spread distribution and by the limited availability of human parathyroid hormone for testing purposes. Of the sera tested, only 5 were selected as having high titre and sensitivity for low concentrations of human parathyroid hormone. The 5 antisera were further evaluated for amino- and carboxyl-region specificities for the human parathyroid hormone in comparison with antiserum 211/32, widely distributed for use in radioimmunoassay for clinical purposes. The selected antisera appear to be of high affinity with good recognition of the whole or carboxyl-region parts of the human parathyroid molecule.

Non-ginsenoside nicotinic activity in ginseng species.

Amongst the many different therapeutic applications of ginseng are beneficial effects on age-related cognitive impairments. Ageing in the brain is associated with a loss of nicotinic receptor binding and receptor stimulation increases binding. Stimulation of the CNS (central nervous system) nicotinic receptor is considered to be beneficial in relation to symptomatic treatment and neuroprotection in age-associated cognitive disorders which involve a further receptor loss. We assessed Panax ginseng, Panax quinquefolium and several chemical constituents of these plants for nicotinic activity based on displacement of 3H-(-)nicotine from human brain cerebral cortex membranes in vitro. Dose-dependent displacement was evident in crude ethanol extracts of Panax ginseng and Panax quinquefolium. Assay of an extract of Panax ginseng showed the plant to have affinity for both the nicotinic receptor, and to a lesser extent the muscarinic receptor (IC50 2.12 mg/mL and 5.25 mg/mL respectively). Activity was largely conserved after the extraction of choline and other water soluble quaternary ammonium compounds (QAC), indicating that the activity of the plant extracts was not due to choline. Displacement binding assay of some purified chemical constituents, including a number of ginsenosides, showed that these were not primarily responsible for Panax activity. The active chemical constituent has yet to be identified, but the demonstrated nicotinic activity of ginseng warrants further investigation with reference to therapeutic activity in age-related conditions such as dementia.

Renal effects of ACE inhibition in ovine heart failure: a comparison of intermittent and continuous ACE inhibition.

Results of uncontrolled studies suggest that the duration of action of an ACE inhibitor may be an important determinant of renal impairment when using these agents to treat patients with heart failure. To determine whether there is experimental evidence for this hypothesis, we compared the effects of intermittent (captopril, 25 mg i.v. bolus twice daily) and continuous (captopril. 25 mg bolus, then 50 mg/day by constant infusion) ACE inhibition in an ovine model where heart failure was induced by rapid left ventricular pacing (LVP). Six sheep underwent three 4-day periods of LVP with intermittent, continuous, or no treatment (control) given in random order from the onset of LVP. Despite evidence that intermittent captopril administration allowed significant recovery of serum ACE activity (4.6 +/- 1.2 vs. 1.1 +/- 0.5 pmol/L before and after captopril bolus on day 4, p less than 0.001) and restitution of arterial pressure between successive boluses (48 +/- 7 vs. 41 +/- 4 mm Hg, p less than 0.01), there was no difference in the renal effects of intermittent and continuous ACE inhibition (creatinine clearance was 44 +/- 14 and 47 +/- 8 ml/min on day 4 of the intermittent and continuous phase, respectively). Nevertheless, there was a significant correlation between the decline in arterial pressure and fall in creatinine clearance induced by ACE inhibition (r = 0.65, p less than 0.05), with evidence that drug accumulation may potentiate hypotension and renal impairment should arterial pressure be reduced below the threshold for renal autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Extreme hypoventilation reduces ventilator-induced lung injury during ventilation with low positive end-expiratory pressure in saline-lavaged rabbits.

OBJECTIVE: To compare the degrees of ventilator-induced lung injury caused by two ventilation protocols. DESIGN: Randomized trial. SETTING: University animal laboratory. SUBJECTS: Sixteen New Zealand white rabbits. INTERVENTIONS: After five sequential saline lung lavages, eight pairs of anesthetized rabbits were allocated randomly to receive either of two ventilation protocols for 4 hrs during neuromuscular blockade. Both groups received 3 cm H2O of positive end-expiratory pressure and 100% oxygen. Control group animals received an estimated tidal volume of 12 mL/kg, an inspiratory time of 0.7 sec, and a ventilatory rate adjusted for a PaCO2 of 35 to 45 torr (4.7 to 6 kPa). Study group animals were ventilated through an intratracheal catheter, with inspiratory time of 1.5 secs, ventilatory rate of 20 breaths/min, and peak inspiratory pressure of 4 to 8 cm H2O, adjusted to maintain PaCO2 at 150 to 250 torr (20 to 33 kPa). MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured every 30 mins. After 4 hrs, a final lung lavage was performed. Physiologic parameters, cell counts and protein concentration in the final lavage, and lung histology were compared between groups. The alveolar-arterial oxygen tension gradient was higher in the study group over the first 1.5 hrs, but the time profile showed significantly (p = .001) greater improvement in the study group. After 4 hrs, the mean alveolar-arterial oxygen tension gradient was lower in the study group (94 torr [12.5 kPa] vs. 201 torr [26.8 kPa]). The increase in neutrophil count from the initial to the final lung lavage was lower in the study group (0.27 x 10(7) cells/L vs. 2.01 x 10(7) cells/L, p = .037), as was the absolute value of the neutrophil count in the final lavage (1.33 x 10(7) cells/L vs. 3.02 x 10(7) cells/L, p = .04). The median hyaline membrane score was lower in the study group (0.5 vs. 3.0) but the difference was not statistically significant. CONCLUSION: These findings suggest that a very low tidal volume reduces ventilator-induced lung injury in saline-lavaged rabbits during ventilation at low lung volume.

Evidence for quark-hadron duality in the proton spin asymmetry A1.

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry A1. Longitudinally polarized positrons were scattered off a longitudinally polarized hydrogen target for values of Q2 between 1.2 and 12 GeV2 and values of W2 between 1 and 4 GeV2. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable x. This finding implies that the description of A1 in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of Q2 above 1.6 GeV2.

Q2 dependence of nuclear transparency for exclusive rho0 production.

Exclusive coherent and incoherent electroproduction of the rho(0) meson from 1H and 14N targets has been studied at the HERMES experiment as a function of coherence length (l(c)), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon (-Q2). The ratio of 14N to 1H cross sections per nucleon, called nuclear transparency, was found to increase (decrease) with increasing l(c) for coherent (incoherent) rho(0) electroproduction. For fixed l(c), a rise of nuclear transparency with Q2 is observed for both coherent and incoherent rho(0) production, which is in agreement with theoretical calculations of color transparency.