Cerebrospinal fluid levels of alpha-tocopherol in amyotrophic lateral sclerosis

We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 30 patients with sporadic amyotrophic lateral sclerosis (SALS) and 78 matched controls. The mean CSF and serum vitamin E levels did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal versus bulbar) of SALS. CSF alpha-tocopherol levels did not correlate with age, age at onset, and duration of the disease. These results suggest that CSF and serum alpha-tocopherol concentrations are unrelated with the risk for ALS.     

Normal and abnormal embryonic development of the anorectum in human embryos

A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self-organization, and natural selection drives formation of malignant phenotype. This concept offers a novel perspective for investigation of tumorigenesis without invalidating current molecular findings. The essay integrates the ideas of the sciences of complexity in a biological context.     

Vascular anatomy at the ureteropelvic junction

In roosters, fertility peaks to 96% at 32 weeks, shortly after sexual maturation, and then declines rapidly to 68% at 70 weeks and to less than 10% at 110 weeks, as a result of intratesticular retention of spermatozoa. The reduction in fertility is associated with functional structural changes of the interstitial tissue, reflected in decreased plasma androgen levels from 2.7 ng/ml at 32 weeks to less than 0.5 ng/ml at 110 weeks. In high fertility roosters, the interstitial tissue is tightly packed with Leydig cells, which contain relatively large amounts of rough endoplasmic reticulum and lipid droplets, both related to androgen synthesis. In the old rooster, which has a low fertility, the interstitial tissue contains only occasional Leydig cells within an enlarged intercellular space. These Leydig cells contain small amounts of endoplasmic reticulum, mainly rough, and there are low plasma androgen levels. It is concluded that differentiation of roosters' interstitial tissue is reflected by plasma levels of androgen. This, in turn, is related to the mechanism of spermatozoa release from Sertoli cells and, consequently, with the level of fertility.     

Eradication of Helicobacter pylori by triple therapy in ulcerous patients: the role of endoscopy and antibiotic sensitivity

BACKGROUND: A protocol was conducted to evaluate the compliance and results of Helicobacter pylori infection treatment in patients with ulcer disease. To know the metronidazole, clarithromycin and amoxicillin activities of Helicobacter pylori strains from such patients. PATIENTS AND METHODS: 35 patients with ulcer disease (27 duodenal ulcer and 8 gastric ulcer) were studied. Diagnosis of Helicobacter pylori infection was performed by urease test and culture of mucosal gastric samples from patients undergoing endoscopy. The patients received the following treatment during 7 days: omeprazole (20 mg bid), clarithromycin (500 mg bid) and amoxicillin (1 g bid), OCA x 7. Susceptibility was determined by E-test system on Wilkins-Chalgren blood agar and read after 5 days. RESULTS: 22/24 patients who had completed the protocol design eradicated Helicobacter pylori (91.7%), 11 patients (31.4%) refused second endoscopy to verify control of eradication. After treatment 10 patients presented with pyrosis "de novo" (28%). The overall metronidazol, claritromycin and amoxicillin resistance rate was 50%, 1.5% and 0% respectively. CONCLUSIONS: OCA x 7 treatment obtains a eradication rate higher than 90% in our patients with ulcer disease, despite smoking habit, but with a significative number of patients presenting pyrosis after treatment. We recommend a non-endoscopy method to verify eradication rate, because of its poor acceptance. 3. Metronidazol resistance rate is high in our series but clarithromycin susceptibility is maintained.     

Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior vena cava occlusion

BACKGROUND: Renal ischemia is produced during orthotopic liver transplantation when the inferior vena cava is clamped above the renal veins (inferior vena cava occlusion [IVCO]), and it often leads to postoperative renal failure. Although free radicals and nitric oxide (NO) have been implicated in the pathogenesis of ischemic renal failure, the effect of free radical scavengers in this model is unknown. METHODS: The effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, on the acute renal failure that follows IVCO were evaluated in pentobarbital-anesthetized dogs. The effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester (NAME) was also studied. Renal vascular endothelial function was tested by infusing acetylcholine (Ach) into the renal artery before the ischemia and during reperfusion. RESULTS: Renal failure developed during IVCO and persisted during reperfusion in all groups. However, in NAC-pretreated dogs, the glomerular filtration rate recovered progressively, reaching 31% of basal preischemic values 150 min after reperfusion. During reperfusion, fractional excretion of sodium increased above preischemic values only in the control group, which indicates a beneficial effect of NAC and NAME on the tubular dysfunction observed during reperfusion. The renal response to Ach was abolished in control dogs and in animals given NAME during reperfusion, which indicates endothelial dysfunction. However, in NAC-pretreated dogs, the renal response to Ach was preserved during reperfusion. CONCLUSIONS: These results demonstrate that NAC ameliorates the renal failure and renal endothelial dysfunction induced by IVCO. This protective effect was abolished by NAME, which suggests that NO is involved in the beneficial effects of NAC. These data also suggest that the use of NAC could be beneficial in ameliorating the acute renal failure observed after orthotopic liver transplantation.     

Diagnosing coronary arterial stent thrombosis and arterial closure

This single-center review of a consecutive series of patients requiring reexamination by angiography within 1 week of a coronary stent placement due to chest pain reveals that patients treated with a poststent anticoagulation regimen of warfarin and aspirin, and those with lower poststent deployment dilation pressures, have an increased risk of subacute stent thrombosis. Repeat cardiac catheterization within the first week after coronary artery stent implantation should be reserved for patients with significant electrocardiographic changes.     

A prospective randomized trial comparing the use of omeprazole-based dual and triple therapy for eradication of Helicobacter pylori

BACKGROUND: Controversy surrounds the optimal composition, dosage, and duration of therapies for eradication of Helicobacter pylori. We prospectively compared omeprazole-based dual and triple therapies in the eradication of H. pylori in a randomized manner. METHODS: Between June 1995 and March 1997, 1000 consecutive patients with acid-peptic disease associated with H. pylori infection (duodenal ulcer, 388 patients, gastric ulcer, 179 patients; duodenitis, 173 patients; gastritis, 260 patients) were prospectively recruited. They were randomized to either a 2-wk (OA) course of omeprazole 20 mg and amoxicillin 1 g, both given twice daily, or treatment for 1 wk (OCM) with omeprazole 20 mg once daily, clarithromycin 500 mg twice daily, and metronidazole 400 mg twice daily. RESULTS: The age of these 1000 patients ranged from 16 to 90 yr, with a mean of 54.9 yr. Side effects occurred in 29.6% (95% confidence interval [CI] 25.6-33.8%) and 10.6% (95% CI 8.0-13.6%) of patients taking OCM and OA, respectively (p < 0.0001). Apart from taste disturbance, however, there were no significant differences in the incidences of side effects between the two groups. One patient in the OA group and four patients of the OCM group could not tolerate the medications, and therefore did not complete treatment (p = 0.37). Seven and 13 patients in the OA and OCM groups, respectively, refused a second endoscopy (p = 0.25). The remaining 975 patients underwent a second endoscopy. Positive endoscopic findings were significantly more common in the OA group (51/492; 10.4%; 95% CI 7.8-13.4%) than in the OCM group (25/483; 5.2%; 95% CI 3.4-7.5%) in the per-protocol (PP) analysis (p = 0.004). On intent-to-treat (ITT) analysis, the overall eradication rates in the OA and OCM groups were 73.6% (95% CI 69.5-77.4%) and 92% (95% CI 89.3-94.2%), respectively (p < 0.0001). On PP analysis, the corresponding rates were 74.8% (95% CI 70.7-78.6%) and 95.2% (95% CI 92.9-97.0%), respectively (p < 0.0001). CONCLUSIONS: A course of omeprazole, clarithromycin, and metronidazole for 1 wk is a safe, well-tolerated, efficacious, and cost-effective treatment for H. pylori infection.     

Paleopathology in osseous remains from the 16th century. A survey of rheumatic diseases

OBJECTIVE: To describe the rheumatic conditions found in skeletal remains of Amerindian ancestry disinterred from a 16th century Mexican cemetery. METHODS: A physical anthropologist and 2 rheumatologists surveyed the recovered skeletal remains. RESULTS: We examined the skeletal remains of 443 subjects. We found 19 cases of Pott's disease, 17 of osteoarthrosis in various anatomical locations, 2 spondyloarthropathies, probably ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis, one probable septic arthritis in the stemoclavicular joint, and 2 compression fractures of the spine. We found no cases of gout or rheumatoid arthritis. CONCLUSION: This is the first report on the presence of rheumatic conditions in colonial Mexico. Studying the remains of these populations can provide useful information about the origin and evolution of different rheumatic conditions.     

The spectrum of acridine resistant mutants of bacteriophage T4 reveals cryptic effects of the tsL141 DNA polymerase allele on spontaneous mutagenesis

Mutations in the ac gene of bacteriophage T4 confer resistance to acridine-inhibition of phage development. Previous studies had localized the ac gene region; we show that inactivation of T4 Open Reading Frame 52.2 confers the Acr phenotype. Thus, 52.2 is ac. The resistance mechanism is unknown. The ac gene provides a convenient forward mutagenesis assay. Its compact size (156 bp) simplifies mutant sequencing and diverse mutant types are found: base substitutions leading to missense or nonsense codons, in-frame deletions or duplications within the coding sequence, deletion or duplication frameshifts, insertions, complex mutations, and large deletions extending into neighboring sequences. Comparisons of spontaneous mutagenesis between phages bearing the wild-type or tsL141 alleles of DNA polymerase demonstrate that the impact of the mutant polymerase is cryptic when total spontaneous mutant frequencies are compared, but the DNA sequences of the ac mutants reveal a substantial alteration of fidelity by the mutant polymerase. The patterns of base substitution mutagenesis suggest that some site-specific mutation rate effects may reflect hotspots for mutagenesis arising by different mechanisms. A new class of spontaneous duplication mutations, having sequences inconsistent with misaligned pairing models, but consistent with nick-processing errors, has been identified at a hotspot in ac.