Five-year follow-up pulmonary function studies in patients with anti-trypsin deficient pulmonary emphysema]

Five-year follow-up study was carried out in pulmonary emphysematous patients with intermediate antitrypsin deficiency. The examinations showed no deterioration in the clinical state of the patients but in some parts of the controlled functional parameters a statistically significant worsening was found in this period of study.     

Early stress tests following an uncomplicated myocardial infarct: a comparison between symptom-limited and submaximal tests

To compare the diagnostic and prognostic usefulness of symptom-limited versus load-limited submaximal stress testing, 76 patients, during the first week post acute non-complicated myocardial infarction, were submitted to a symptom-limited Naughton-modified protocol stress test. At 2 METs, 3 METs and maximal effort levels, the tests were classified as positive or negative following the currently used criteria. After a mean follow-up of 15 months, the symptom-limited protocol showed the best sensitivity (95%), specificity (78%), positive (64%) and negative (98%) predictive value, and also the highest risk ratio (27.4) for prediction of subsequent coronary events (2p less than 0.01 vs 2 METs, 3 METs and 2D-Echocardiogram results). Forward stepped multiple correlation analysis indicated independent prognostic value for the results of the symptom-limited stress test (R2: .52 p less than 0.01) and for the location of the myocardial infarction (R2: .05 p less than 0.05) only. In addition, the discriminant prognostic power of the symptom-limited protocol was significant after the fourth month of follow-up (2p less than 0.05 vs submaximal tests and 2D-Echo). Therefore, we recommend the performance of a symptom-limited stress test during the first week post acute non-complicated myocardial infarction, provided that all coronary active medication has been withheld 24 hours before the test.     

Benzamide potentiation of the cytotoxicity of bifunctional galacticol in resistant P388 leukemia correlates with inhibition of DNA ligase II

Summary Benzamide (BA) enhances the cytotoxicity of 1,2:5,6-dianhydrogalactitol (DAG) in resistant P388 leukemia cell lines but not in the sensitive parent line. To examine the reason for this difference in response, we carried out an alkaline elution assay using proteinase K to study DNA interstrand cross-linking. At early time points, equal concentrations of DAG produced the same level of interstrand cross-linking (ICL) in the resistant and sensitive P388 leukemic cells, although marked differences were observed in their cytotoxicity toward the two cell lines. In the sensitive cells, neither the amount of DNA cross-linking nor the cytotoxicity changed during the observation period (38 h) in either the presence or the absence of BA. In contrast, the elution rate of the DNA of DAG-treated resistant cells increased with time and had reached the control levels by 38 h. However, when these cells were postincubated with BA for 38 h, the elution rate of DNA was much faster than that observed for the untreated resistant cells, indicating an accumulation of DNA singlestrand breaks (SSB). The SSB accumulation caused by BA was associated with an inhibition of the activity of ligase II enzyme, which was stimulated when resistant cells were treated with DAG alone. The potentiating effect of BA on the resistant cells can thus be related to the inhibiting action of BA on the DNA-rejoining enzyme, ligase II. The lack of sensitization by BA of the DAG-treated parent cell line may be attributable to the absence of DNA-SSB formation, which is necessary for ligase II activation through the stimulation of poly(ADP-ribose) synthesis.     

Alcohol recidivism impairs long-term patient survival after orthotopic liver transplantation for alcoholic liver disease.

The aim of this study was to evaluate the rate of alcohol recidivism after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) and its influence on the allograft and patient survival, as well as the development of comorbidities and de novo cancers. The study was performed on 54 subjects previously analyzed and transplanted in our center for ALD, whose follow-up was prolonged to a mean of 99.2 (SD 31.7) months (range, 14-155). Medical records were reviewed, and data on alcohol consumption, therapeutic compliance, graft evolution, rejection, infections, comorbidities, rates of de novo malignancies and other clinical events, and survival were collected. Comparisons between groups were performed by the Fisher's exact test, and survival was assessed by the Kaplan-Meier method. Survival curves were compared using the Mantel-Cox statistic. The risk of death resulting from alcohol recidivism was analyzed with a Cox proportional hazards model. Fourteen patients who underwent transplantation for ALD (25.9%) returned to alcohol use between 5.0 and 86.9 months after OLT (median, 47.5). There was no significant association between the presence or absence of alcohol recidivism and the occurrence of graft rejection, infections, associated comorbidities after OLT, or compliance. The 5- and 10-year survival rates for patients with alcohol recidivism were 92.9% and 45.1%, respectively, compared with 92.4% and 85.5%, respectively, for patients without alcohol recidivism. These figures show significantly lower survival rates in recidivistic patients after 10 years (P < 0.01, Mantel-Cox). The fact that patients who resumed alcohol consumption have a worse 10-year survival rate might be attributed to a higher frequency of deaths, primarily from cancer and cardiovascular events.     

Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver.

Apolipoprotein-B 48 (apoB 48) and apoB 100 expression and the editing of apoB mRNA have previously been shown to be hormonally regulated in rat liver. We have investigated the effects of hypophysectomy and replacement therapy with T4, cortisol (C), and GH in vivo on the proportion of edited apoB mRNA in rat liver and cultured rat hepatocytes as well as the synthesis and secretion of apoB 48 and apoB 100 in cultured rat hepatocytes. Hypophysectomy decreased the proportion of edited apoB mRNA in intact liver from 62% in normal rats to 29% in hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C did not influence the proportion of edited apoB mRNA, whereas treatment with GH, either alone or together with T4 and C, increased the proportion of edited apoB mRNA to the levels observed in normal rats. In cultured hepatocytes isolated from normal rats, the proportion of apoB 48 (percentage of total labeled apoB) was 78% and decreased to 40% in cells isolated from hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C had no effect on the proportion of apoB 48 present in isolated cells, whereas it increased to 60% after treatment with GH together with T4 and C. The proportion of apoB 48 in the medium was affected by hypophysectomy and the various hormonal treatments in a similar way to that observed in the cells. Results from in vivo labeling experiments suggested that GH alone had the capacity to increase the percentage of apoB 48 in hypophysectomized rats. On the contrary, T4 and C was needed, in addition to GH, to increase the proportion of apoB 48 in isolated hepatocytes from hypophysectomized rats. Our results suggest that this discrepancy is due to a difference between the effect of GH alone on apoB mRNA editing in the intact liver and that in isolated hepatocytes. The total secretion of apoB into the cell culture medium was not affected by hypophysectomy and hormonal treatments of the rats. In conclusion, these results indicate that GH is involved in the regulation of editing of apoB mRNA and the proportion of apoB 48 synthesized and secreted in rat liver. Thus, our observations emphasize the importance of GH as a regulator of lipoprotein metabolism.     

Bromazepam-induced dystonia.

Benzodiazepines are drugs with a good tolerance that are widely used for the treatment of anxiety. Extrapyramidal side-effects are unusual. Diazepam is effective for the treatment of drug-induced dystonias, nevertheless there are some reports of Diazepam-induced dystonia. We report a case history of a patient who developed oromandibular dystonia after taking Bromazepam. The possible mechanisms that cause drug-induced dystonia are described.     

Polynuclear nickel hexacyanoferrates: monitoring of film growth and hydrated counter-cation flux/storage during redox reactions

An electrochemical quartz crystal microbalance (EQCM) was employed to monitor directly the growth of nickel(II) hexacyanoferrate(III) (NiHCNFe) films on gold substrates during electrodeposition as well as a result of sol-gel aggregation in colloidal nickel ferricyanide solutions used for modification. Frequency changes due to mass changes of the gold/crystal working electrode were correlated with cyclic voltammetric (CV) data. Evidence is also provided for the sorption of counter-cations (Li⁺, Na⁺ and K⁺), and associated water molecules, during redox reactions of the film. There is a strict relationship between the amount of alkali metal ions incorporated into the film during reduction, or excluded from the film during oxidation, and the frequency changes during EQCM measurements. The amount of solvent (H₂O) transferred and sorbed in the NiHCNFe film reflects the degree of hydration of the investigated counter-ions. Anions also seem to participate in NiHCNFe electrochemistry, but their role is much less pronounced.     

Intraocular pressure effects on optic nerve-head oxidative metabolism measured in vivo

The effects of acute intraocular pressure (IOP) on the reduction/oxidation ratio of cytochromea,a ₃ were measured from intact cat optic nerve by microfiber reflection spectrophotometry. This enabled the real-time analysis of optic nerve-head oxidative metabolism following IOP or mean arterial pressure (MAP) changes. Findings included: (1) cytochromea,a ₃ became more reduced and relative blood volume decreased at lower perfusion pressures, even at IOP of <20 mm Hg; (2) metabolic inhibition began at variable perfusion pressures but invariably progressed as perfusion pressure declined; and (3) increased IOP or decreased MAP caused metabolic inhibition. These findings demonstrate that: (1) optic nerve metabolic dysfunction is possible at low IOPs; (2) lowering IOP can reverse metabolic dysfunction; (3) the metabolic response is dependent on IOP and/or MAP changes; and (4) the metabolic inhibition is related to optic nerve ischemia. Presented at the 8th International Congress of Eye Research-Symposium on Retinal Oxygenation, San Francisco, September 1988