Theophylline treatment in the extubation of infants weighing less than 1,250 grams: a controlled trial

The role of theophylline in weaning infants weighing less than 1,250 g at birth from mechanical ventilation was evaluated. Infants were randomized into control or theophylline treatment groups when they required minimal ventilatory support (peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 2 cm H2O, rate 12 breaths per minute, and FiO2 less than 0.3), and they were extubated 24 hours later. Infants required reintubation if they had (1) PaCO2 greater than 55 mm Hg and pH less than 7.20, (2) FiO2 greater than 0.5, or (3) apnea associated with a heart rate less than 100 beats per minute that required frequent stimulation (more than 20 episodes during a 16-hour period). Among 32 infants (birth weight less than 1,000 g) who reached minimal ventilatory support before seven days after delivery, 13 of 18 (72%) control infants required reintubation, whereas only four of 14 (28%) theophylline-treated infants required reintubation. On the other hand, among infants (birth weight less than 1,000 g) who reached minimal ventilatory support after seven days following delivery, only one of six (17%) of the control group required reintubation and no improvement could be seen with theophylline treatment. Similarly, among control infants (birth weight 1,001 to 1,250 g), only ten of 45 (23%) required reintubation after reaching low intermittent manditory ventilation settings. In summary, most infants recovering from respiratory distress syndrome who had birth weights (1) greater than 1,000 g or (2) less than 1,000 g and who were older than seven days could be successfully extubated from minimal ventilatory support without theophylline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevation of arterial potassium during acute systemic hypoxia is abolished by alkalosis

BACKGROUND: Small elevations in plasma potassium evoke vasodilation in the peripheral circulation. Systemic hypoxia elevates arterial potassium and also modifies arterial pH. AIMS: We examined the interaction between pH and potassium in blood during systemic hypoxia and the effect of pH on the uptake/release of potassium in the peripheral tissues. METHODS: Anesthetized dogs were ventilated with air plus oxygen for normoxia or air plus nitrogen for hypoxia. Some animals received intravenous sodium bicarbonate to elevate pH by 0.1 units. Arterial plasma potassium concentration was measured in normoxia and hypoxia. A rat gracilis muscle was perfused with normoxic Krebs buffer and the potassium content of the venous outflow was compared during perfusion at pH 7.4, 6.8, or 7.8. RESULTS: In dogs with an arterial pH of 7.40-7.45, systemic hypoxia elevated the arterial potassium by 1 mmol/L. An arterial pH of 7.55 did not alter the basal potassium concentration, but it abolished the hypoxia-induced increase. In rat muscle, reduction of the perfusate pH from 7.4 to 6.8 reduced arterial perfusion pressure from 8.73 to 7.32 kPa and venous potassium from 6.6 to 5.2 mM. Elevation of perfusate pH to 7.8 decreased the arterial perfusion pressure from 8.44 to 6.95 kPa but did not affect venous potassium. CONCLUSIONS: The hypoxia-induced elevation of arterial potassium is abolished by increasing the pH to 7.55. This is not due to enhanced potassium uptake into peripheral tissues at high pH. Red blood cells are suggested as the most likely source of the potassium released in hypoxia.     

Biotinidase catalyzes debiotinylation of histones

Summary Background Posttranslational modifications of histones play important roles in processes such as regulation of gene expression and DNA repair. Recently, evidence has been provided that histones in human cells are modified by covalent attachment of biotin. Aim of the study To determine whether the reverse process (debiotinylation of histones) occurs in biological samples and whether debiotinylation is an enzyme-mediated process; and to characterize the enzyme that mediates debiotinylation of histones. Methods Plasma and lymphocytes from healthy adults and a biotinidase-deficient patient were used as sources of debiotinylating enzymes. Debiotinylation of histones by plasma and lymphocyte proteins was measured using a colorimetric 96-well plate assay. Results Histones were debiotinylated rapidly if incubated with human plasma or lysates of lymphocytes. The following observations are consistent with the hypothesis that debiotinylation is an enzyme-mediated process: (i) Hydrolysis was slower at 4 °C compared to 37 °C; (ii) debiotinylating activity was destroyed when biological samples were heated at 90 °C for 30 min preceding incubation with biotinylated histones; and (iii) rates of debiotinylation were pH dependent. Rates of histone debiotinylation were significantly decreased in biotinidase-deficient samples. Conclusion Debiotinylation of histones in human samples is an enzyme-mediated process that is at least partly catalyzed by biotinidase. Received: 27 September 2001, Accepted: 6 January 2002     

Effect of parietal lobe lesions on saccade targeting and spatial memory in a naturalistic visual search task

The eye movements of two patients with parietal lobe lesions and four normal observers were measured while they performed a visual search task with naturalistic objects. Patients were slower to perform the task than the normal observers, and the patients had more fixations per trial, longer latencies for the first saccade during the visual search, and less accurate first and second saccades to the target locations during the visual search. The increases in response times for the patients compared to the normal observers were best predicted by increases in the number of fixations. In order to investigate the effects of spatial memory on search performance, in some trials observers saw a preview of the search display. The patients appeared to have difficulty using previously viewed information, unlike normal observers who benefit from the preview. This suggests a spatial memory deficit. The patients' deficits are consistent with the hypothesis that the parietal cortex has a role in the selection of targets for saccades, in memory for target location.     

Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine

Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (> 20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.     

Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs

Exogenous insulin-like growth factor (IGF)-I has been shown to increase growth rate in neonatal pigs while an analogue of IGF-I, long arginine (LR3) IGF-I, has been shown to be more potent than IGF-I in the rat. Therefore, two studies were conducted to determine whether IGF-I and LR3IGF-I increase growth in the artificially-reared neonatal pig. Expt 1 involved forty-two (2 kg initial weight) pigs infused with either control, IGF-I (2, 4 or 8 microg/h) or LR3IGF-I (2, 4 or 8 microg/h) infusions for 8 d. Pigs were weighed and then offered 1.7 MJ (gross energy) milk replacer/kg0.75 per d. Expt 2 involved eighteen pigs (2 kg initial weight) treated with control saline, IGF-I (8 microg/h) or LR3IGF-I (8 microg/h) infusions. After 9 d an additional pump was inserted to increase the infusion rates of each of the growth factors (16 microg/h) for a further 9 d. Cows' milk was provided ad libitum. In Expt 1 there was no overall effect of growth factors on daily weight gain or slaughter weight. However, milk intake was greater in pigs infused with growth factors (909 v. 867 g/d, P=0.027), with an apparently greater milk intake by the pigs infused with IGF-I compared with LR3IGF-I (920 v. 898 g/d, P=0.12). Infusion of LR3IGF-I decreased plasma IGF-I concentrations, but had no effect on plasma IGF-II concentrations. In Expt 2, neither IGF-I nor LR3IGF-I infusion had any effect upon daily weight gain over the first 9 d of the study. However, over the second 9 d of the study, daily weight gain was increased in LR3IGF-I-infused pigs (457 v. 386 g/d, P<0.01), but not in pigs infused with IGF-I (413 v. 386 g/d, P=0.15). Milk intake was not different during the first 9 d of the study but was significantly greater in pigs infused with growth factors over the second half of the study (3407 v. 2905 g/d, P<0.01). Plasma IGF-binding protein-3 concentrations were highly correlated (R=0.85) with average daily gain over the 3 d preceding blood sampling. In conclusion, exogenous IGF-I and particularly LR3IGF-I can increase growth rate and milk intake in artificially-reared pigs fed ad libitum but not in limit-fed piglets.     

Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.     

Observations on the microbiology of urethritis in black South African men

The occurrence of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium was determined by molecular techniques in urine specimens from 182 black South African men who had symptoms and/or overt signs of urethritis. Eighty-six (47.3%) of these men were infected with N. gonorrhoeae. There were 185 men without overt evidence of urethritis, 16 (8.6%) of whom were also infected with N. gonorrhoeae. Of the 96 men who had non-gonococcal urethritis, 14 (14.6%) were infected with C. trachomatis, 16 (16.7%) with M. genitalium and only one with both microorganisms. In comparison, 15 (8.9%) of 169 men without overt urethritis and without N. gonorrhoeae were infected with C. trachomatis and 15 (8.9%) with M. genitalium, proportions that were about half the size of those in the group with overt urethritis.     

Effect of dopamine D3 antagonists on PPI in DBA/2J mice or PPI deficit induced by neonatal ventral hippocampal lesions in rats.

Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animal models such as the test of prepulse inhibition of startle response (PPI) in rodents. It has been found that antipsychotics enhanced PPI in DBA mice and reversed the PPI deficit induced by neonatal ventral hippocampal (NVH) lesions in rats. However, the relative involvement of D(3) and D(2) receptors in these effects is unknown since all antipsychotics are D(2)/D(3) antagonists with limited binding preference at D(2) receptors. Therefore, in the current study, we investigated the influence of several dopamine antagonists with higher selectivity at D(3) vs D(2) receptors on PPI in DBA/2J mice and in NVH-lesioned rats. The PPI in DBA/2J mice was enhanced by the nonselective D(2)/D(3) antagonists, haloperidol at 0.3-3 mg/kg, or risperidone at 0.3-1 mg/kg, while PPI-enhancing effects were observed after the administration of higher doses of the preferential D(3)/D(2) antagonist, BP 897 at 8 mg/kg, and the selective D(3) antagonists, SB 277011 at 30 mg/kg and A-437203 at 30 mg/kg. No effect was observed following the treatment with the selective D(3) antagonist, AVE 5997 up to 30 mg/kg. The PPI deficits induced by NVH lesions were reversed by haloperidol but not by the more selective D(3) antagonists, A-437203 and AVE 5997. BP 897 enhanced PPI nonselectivity, that is, in both lesioned and nonlesioned rats. In summary, the present study indicates that PPI-enhancing effects induced by antipsychotics in DBA/2J mice and in NVH-lesioned rats are unlikely to be mediated by D(3) receptors.     

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. Method:- A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.