The effect of catalase inhibitor 3-amino-1,2,4-triazole on coupled oxidative phosphorylation and the state of adenyl system in liver mitochondria of albino rats

Blepharoptosis is a recognized complication of cataract extraction and other ocular procedures. A 6-month waiting period is recommended before repairing postcataract ptosis because most cases resolve during this time. We report the course of a patient who developed spontaneous recovery of eyelid function 11 months after cataract surgery. She had previously undergone successful ptosis repair 8 months after cataract extraction, but developed overcorrection 3 months later as her levator function returned to normal. We recommend at least a 1-year waiting period before repair of postcataract ptosis. If corrective surgery is undertaken earlier than 1 year due to visual obstruction or for aesthetic reasons, we suggest two guidelines. The levator should be plicated rather than resected and patients should be forewarned of the possibility for a revisionary procedure if spontaneous return of levator function occurs.     

Free protein S deficiency in patients with Crohn's disease

Multifocal intestinal infarctions, due to thrombosis in small vessels, might be a pathogenetic mechanism for Crohn's disease (CD). Deficiency of free protein S may contribute to the development of such thrombotic occlusions. In the present study free protein S was measured in 54 patients with CD. In 31 patients (57.4%) the plasma concentrations of free protein S were below the lower normal range. The mean value of free protein S in CD patients was 72.2%, as compared with 97.5% in healthy subjects (p < 0.01). The concentrations of C4b-binding protein and protein C were similar in the two groups. Free protein S levels were not correlated to disease activity, previous surgery or complications, extraintestinal manifestations, or current medical therapy. The impairment of the protein S/protein C/thrombomodulin system found in patients with CD favours coagulation and might be of importance for both the development of CD and its thromboembolic complications.     

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.     

Effects of oxygen on 3-hydroxyanthranilate oxidase of the kynurenine pathway

Iron containing 3-Hydroxyanthranilate oxidase (3HAO) converts 3-hydroxyanthranilate (3HAA) and dioxygen into a precursor which spontaneously converts to quinolinic acid (QA). 3HAO participates in de novo biosynthesis of NAD in mammalian kidney and liver, and it is present in low concentrations in brain where its function is controversial. However, QA increases in spinal fluid and is associated with convulsions in AIDS dementia, Huntington's disease, and CNS inflammation. QA is a known N-methyl, D-aspartate receptor agonist and excitotoxin that causes convulsions when injected into the brain. Hyperbaric oxygen (HBO) also causes convulsions and we investigated the interrelationships among the stimulating and toxic effects of oxygen and the role of iron in vitro using rat liver enzyme which is reported to be identical to brain enzyme and is more abundant. 3HAO requires dioxygen as a substrate but it was inactivated approximately 40% by 5.2 atm HBO in vitro in 15 min. The apparent Km was 2.6 x 10(-4) M for oxygen and 5 x 10(-5) M for 3HAA, and these values did not change for enzyme that was half-inactivated by HBO oxygen. Thus, oxygen-inactivation appears to be all-or-none for individual enzyme molecules. Freshly prepared enzyme was activated about 3-fold by incubation with acidic iron. Iron-staining of 3HAO, separated by gel electrophoresis after partial purification by FPLC, showed that loss of iron and loss of enzyme activity during HBO exposure were correlated. The apparent oxygen Km of 3HAO is far higher than the oxygen concentration in brain cells. Thus, 3HAO is capable of being stimulated initially in animals breathing HBO, and subsequently of being inactivated with potential significance for brain QA and convulsions.     

Separation of septal influences on lordosis, ultrasound production, and body weight

It is well known that macromolecules like albumin are markedly restricted in their passage across the glomerular capillary wall. However, the relative importance of solute size, charge and shape is currently debated since much of the previous work is based on dextran in neutral or charge-modified forms. These polymers have certain drawbacks that make them less suitable for analysis of capillary permeability and the notion of a glomerular charge barrier has therefore been questioned. Moreover, macromolecules larger than albumin (mol. wt. 69,000) have been suggested to pass through nonselective 'shunt' pathways. In order to study glomerular permeability, isolated rat kidneys were perfused with albumin solutions containing trace amounts of two differently radiolabelled isoenzymes of lactate dehydrogenase (LDH) at low temperature to inhibit tubular function. The isoenzymes have similar size (mol. wt. 140,000) and shape but differ in charge, one carrying a negative net surface charge (LDH1, -19) and the other being slightly cationic (LDH5, +2). The urine and perfusate samples were subjected to high pressure liquid chromatography (HPLC) gel-filtration to allow for measurements of intact LDH. The fractional clearance was 0.11% +/- 0.04% for the anionic LDH1 and 0.56% +/- 0.07% for LDH5, whereas that for albumin was 0.21% +/- 0.03% at a glomerular filtration rate of 0.11 +/- 0.01 mL min-1 g-1 kidney wet weight. The results were analysed using a homogenously charged membrane model and are compatible with a charge density of 35 mEq L-1, with 95% confidence interval of 26-41 mEq L-1. These findings suggest a significant glomerular charge selectivity for proteins substantially larger than albumin. The charge density is, however, far less than estimated from dextran studies.     

The unanticipated difficult airway with recommendations for management

PURPOSE: To review the current literature and generate recommendations on the role of newer technology in the management of the unanticipated difficult airway. METHODS: A literature search using key words and filters of English language and English abstracted publications from 1990-96 contained in the Medline, Current Contents and Biological Abstracts databases was carried out. The literature was reviewed and condensed and a series of evidence-based recommendations were evolved. CONCLUSIONS: The unanticipated difficult airway occurs with a low but consistent incidence in anaesthesia practice. Difficult direct laryngoscopy occurs in 1.5-8.5% of general anaesthetics and difficult intubation occurs with a similar incidence. Failed intubation occurs in 0.13-0.3% general anaesthetics. Current techniques for predicting difficulty with laryngoscopy and intubation are sensitive, non-specific and have a low positive predictive value. Assessment techniques which utilize multiple characteristics to derive a risk factor tend to be more accurate predictors. Devices such as the laryngeal mask, lighted stylet and rigid fibreoptic laryngoscopes, in the setting of unanticipated difficult airway, are effective in establishing a patient airway, may reduce morbidity and are occasionally lifesaving. Evidence supports their use in this setting as either alternatives to facemask and bag ventilation, when it is inadequate to support oxygenation, or to the direct laryngoscope, when tracheal intubation has failed. Specifically, the laryngeal mask and Combitube have proved to be effective in establishing and maintaining a patent airway in "cannot ventilate" situations. The lighted stylet and Bullard (rigid) fibreoptic scope are effective in many instances where the direct laryngoscope has failed to facilitate tracheal intubation. The data also support integration of these devices into strategies to manage difficult airway as the new standard of care. Training programmes should ensure graduate physicians are trained in the use of these alternatives. Continuing medical education courses should allow physicians in practice the opportunity to train with these alternative devices.     

Time course of VMN lesion effects on lordosis and ultrasound production in hamsters

Lesions of the ventromedial hypothalamus (VMN) depress lordosis but increase ultrasonic vocalization in female hamsters. These changes are consistent with the behavioral incompatibility of lordosis and ultrasound production and suggest that the VMN coordinates short-term changes in these behaviors. In keeping with past results, unilateral lesions disrupted lordosis responses to contralateral flank stimulation. The change appeared within 15 min after the lesion and was much more rapid than the corresponding effect in rats. For hamsters, these findings support other evidence suggesting VMN mediation of somatosensory, not just hormonal, influences on lordosis. In a companion study, ultrasound rates became depressed within 15 min of bilateral lesion of the VMN, suggesting a role for the VMN in the short-term control of ultrasound production. Calling at later time intervals was facilitated by the lesions. The direction and time course of the lesion effects on lordosis and ultrasound production suggest that the VMN cannot easily account for the behavioral incompatibility of these 2 responses.