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Biomedical subjects

P Lopez

Publications and source records attributed to P Lopez.

At least 73 records · Page 4Linked to original sources
PubMed1995

Vasodilatory effects of propylthiouracil in patients with alcoholic cirrhosis.

BACKGROUND/AIMS: An experimental study has shown that propylthiouracil increases portal blood flow in normal rats. Whether propylthiouracil has a similar effect in patients with alcoholic cirrhosis remains to be demonstrated. The aim of this study was to evaluate the effects of oral propylthiouracil (300 mg) on systemic and portal hemodynamics in patients with alcoholic cirrhosis. METHODS: Plasma propylthiouracil levels were also measured by high performance liquid chromatography in five patients with alcoholic cirrhosis. In eight patients with cirrhosis, mean arterial pressure, cardiac output and portal blood flow were evaluated before and after placebo and propylthiouracil administration. Hemodynamic measurements were performed by the Doppler technique. The plasma peak level of propylthiouracil was achieved at 1.4 +/- 0.1 h in patients with alcoholic cirrhosis. This time was chosen to express hemodynamic changes. RESULTS: Propylthiouracil administration caused a significant increase in portal blood flow (+16.5%, p < 0.05) in patients with alcoholic cirrhosis. This effect was associated with a mild and significant rise in cardiac output (from 5.8 +/- 0.2 to 6.1 +/- 0.3 l/min, p < 0.05) and a decrease in peripheral vascular resistance (from 1171 +/- 69 to 1070 +/- 67 dyn . s-1 . cm-5, p < 0.01). A significant correlation was observed between changes in portal blood flow and peripheral vascular resistance (r = 0.79, p < 0.05). No significant changes were observed after placebo. CONCLUSIONS: Our findings show that propylthiouracil has a vasodilatory effect in patients with alcoholic cirrhosis. We postulate that this effect could be the mechanism by which propylthiouracil decreases hypermetabolic state, and increases oxygen delivery to the liver, in patients with alcoholic liver diseases.

Female↗
PubMed1995

Vitamin B-12 deficiency and malabsorption are highly prevalent in rural Mexican communities.

Vitamin B-12 status of rural Mexicans was evaluated in two studies, 6 y apart. In the first, a single blood sample was collected from children and adults, including pregnant and lactating women. Prevalence of deficient plasma vitamin B-12 values ranged from 19% to 41% among groups, but plasma folate status was normal in all individuals. Breast milk vitamin B-12 concentration was low in 62% of samples. The second study was conducted in 219 children aged 18-36 mo in five communities, whose prevalence of deficient and low plasma vitamin B-12 concentrations, respectively, was 8% and 33% on entry, 3% and 22% 6 mo later, and 7% and 29% 12 mo later. Prevalence of low holotranscobalamin II concentrations, indicating malabsorption of the vitamin, averaged 18-40% across the three same periods. Both vitamin B-12 status indicators differed significantly between communities. The widespread vitamin B-12 deficiency was probably caused by malabsorption, perhaps exacerbated by low dietary intake and, for young children, maternal depletion of the vitamin.

Adult↗
PubMed1995

A cluster of four genes encoding enzymes for five steps in the folate biosynthetic pathway of Streptococcus pneumoniae.

Two genes, sulB and sulC, in a folate biosynthetic gene cluster of Streptococcus pneumoniae were identified after determination of the DNA sequence between two previously reported genes, sulA and sulD, in a cloned segment of chromosomal DNA containing a mutation to sulfonamide resistance. The gene products, SulB and SulC, correspond to polypeptides of 49 and 21 kDa, respectively. SulC has GTP cyclohydrolase activity and catalyzes the first step in the folate biosynthetic pathway. SulB apparently has dihydrofolate synthetase activity in that it complements a folC mutant of Escherichia coli and thus catalyzes the last step in the pathway. Prior work showed that SulA, a dihydropteroate synthase, and SulD, a bifunctional enzyme, catalyze three intervening steps. Mapping of the mRNA transcribed from the operon was consistent with its beginning at a promoter with a -35 site (gTGtCc) and an extended -10 site (T-TG-TAaAAT) and its termination at the end of a hairpin structure, which would give a transcript 3,745 nucleotides in length. SulC showed a considerable conservation of sequence by comparison with proven or putative GTP cyclohydrolases from four unrelated species, with 38 to 53% of the residues being identical. A similar comparison of SulB with dihydrofolate synthetases showed an identity of only 26 to 37%. Overall, comparisons of the five folate biosynthetic enzymes in different species suggest that S. pneumoniae is related more closely to other gram-positive bacteria, less closely to eucaryotes, and least closely to the gram-negative E. coli. The varied arrangements of folate biosynthetic genes in different species imply an early evolutionary period of fluidity in genomic rearrangement.

Amino Acid Sequence↗
PubMed1995

Effects of long-distance running on serum bilirubin.

This study was undertaken to determine the effects of long-distance running on serum bilirubin fractions. Thirteen male ultramarathon runners participating in a 100-km race volunteered for the study. Venous blood samples were obtained shortly before and immediately after the race. Decreased serum haptoglobin levels (-66%) indicated the presence of hemolysis. After accounting for plasma-volume loss, significant post-race increases were found for creatine kinase (+20-fold), creatine kinase-MB (+252%), alanine aminotransferase (+42%), aspartate aminotransferase (+193%), gammaglutamyl transpeptidase (+56%), and glutamate dehydrogenase (+58%) serum activities, suggesting that running causes alterations of both muscle and liver tissues. Serum concentration of total bilirubin was significantly elevated (+106%) following the race, with changes corresponding to both unconjugated (+96%) and conjugated esters (+283%) of the pigment and significant increases in the ratio of esterified to total bilirubin. Our data show that long-distance running causes increases in the different serum bilirubin fractions which can be accounted for both hemolysis and hepatic disturbances.

Adult↗
PubMed1994

The effects of experimental fasciolosis on bilirubin metabolism in the rat.

The effects of subclinical fasciolosis at various stages of its development on bilirubin metabolism were investigated in rats. Studies were carried out at 3 (initial lesions), 6 (parenchymal degeneration), and 11 weeks (biliary localization of the parasite) after infection with an oral dose of 20 metacercariae of Fasciola hepatica. Both bile flow and bile acid secretion were significantly reduced by Weeks 3 and 6 postinfection, while a significantly increased bile flow was found in the 11-week group. Serum concentration of unconjugated bilirubin was elevated at 3-6 weeks postinfection and that of conjugated bilirubin and the esterified/total bilirubin ratio increased in all infected rats. Biliary excretion of bilirubin mono- and diconjugates was maximally increased by 3-6 weeks, remaining elevated at 11 weeks. No significant change in the biliary diconjugate/monoconjugate ratio was found in any of the groups. UDP-glucuronosyltransferase activity was reduced by Weeks 3 and 6. This was accompanied by a significantly lowered liver cytochrome P450 concentration and an elevation in hepatic heme oxygenase activity. Blood hemoglobin concentration was significantly reduced and reticulocyte count increased by 6 and 11 weeks. Our results indicate that enhanced bilirubin production, cholestasis, and a reduced conjugating activity could be responsible for the changes in plasma and bile pigment composition during the acute stage of fasciolosis. Hemolysis and a high bilirubin excretion are maintained when the parasite migrates into the biliary ducts.

Animals↗
PubMed1994

Temperature dependence of lipoxygenase heat inactivation; evaluation with linearly increasing temperature profiles.

A non-isothermal kinetic method for evaluating the temperature dependence of enzyme heat inactivation has been developed from theoretical considerations. By using a non-linear regression software programme and enzyme activity data obtained along linearly increasing temperature profiles, z values of lipoxygenase were obtained in single experiments, substantially reducing time, cost, and labour. The z values so obtained were slightly dependent on heating rate, varying from 4.11 degrees C at a rate of heating of 2.56 degrees C/min to 4.66 degrees C at a heating rate of 1.48 degrees C/min.

Hot Temperature↗
PubMed1994

Co-management of refractive eye surgery.

An onslaught of publicity about refractive surgery has led to considerable patient interest in this corrective procedure. Regardless of the optometrist's cautious view of refractive surgery, it is here to stay. We may not be providing appropriate care to our patients if we discuss only its disadvantages. It is imperative that we, as primary eye care providers, educate ourselves as to the advantages and disadvantages of refractive surgery so we can better educate our patients. It is our responsibility to help them decide if they are, indeed, candidates for refractive surgery. This paper provides basic knowledge to familiarize the practicing optometrist with radial keratotomy and excimer laser photorefractive keratectomy. Patient selection, preoperative evaluation and counseling, and postoperative care are discussed. Communication between the co-managing optometrist and refractive surgeon is imperative.

Cornea↗
PubMed1994

Diurnal fluctuations of portal and systemic hemodynamic parameters in patients with cirrhosis.

A close temporal relationship between higher levels of portal pressure during the night and the peak incidence of acute variceal bleeding has recently been demonstrated in patients with cirrhosis. Because hemodynamic changes may have a role in triggering this hemorrhagic episode, we measured systemic and portal hemodynamic parameters at 4-hr intervals for 24 hr in 12 cirrhotic patients. These results were compared with those obtained in eight healthy subjects. Cardiac output, femoral and portal blood flows were measured by Doppler technique. In cirrhotic patients, heart rate and mean arterial pressure remained constant throughout the whole study period. A marked and significant increase in portal blood flow (917 +/- 248 ml/min) (mean +/- S.D.) as compared with mesor values (649 +/- 114 ml/min, p < 0.001) was observed at midnight. This effect was accompanied by a mild but significant rise of cardiac output (from 6.5 +/- 0.7 to 6.8 +/- 0.7 l/min, p < 0.01) at 2400 hr. A significant correlation between both hemodynamic parameters was found (r = 0.78, p < 0.01). Cosinor analysis showed a significant (p < 0.05) circadian rhythm for both portal blood flow and cardiac output with an acrophase at 0050 hr. In the healthy subjects group, a significant decrease of mean arterial pressure and heart rate was observed at 2400 hr. Cosinor analysis confirmed the presence of significant rhythm for both hemodynamic parameters. In contrast with cirrhotic patients, no significant changes were observed in portal blood flow and cardiac output in healthy subjects. Our results show that in patients with cirrhosis, maximal increases in portal blood flow occur at night.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Mechanical process and growth cartilages. Essential factors in the progression of scoliosis.

This study showed that the worsening of scoliosis was the result of a mechanical phenomenon. The key feature in this mechanical process was the finding that cuneal deformation affects only part of the vertebral body. The onset of scoliotic curvature occurred as a result of intervertebral motions. However, the worsening was essentially caused by deformation of the vertebral bodies. After the onset of scoliosis, the orientations of the vertebrae were modified in all three planes, and as a result, the spine became mechanically unstable. As a result of this mechanical instability, intervertebral pressures no longer were distributed equally but were concentrated at the junction of the growth cartilages of the vertebral body, near the pedicle on the concave side. Osseous growth was perturbed in this area, the vertebra became deformed, and the vertebral body became wedge shaped. These cuneal deformations resulted in a relative change of position between adjacent vertebral bodies and led to a worsening of the scoliotic curve without involving any articular motion. This phenomenon occurred mostly in the apical region because of the geometric shape of the curvature.

Biomechanical Phenomena↗
PubMed1993

Lymphoproliferative disease of "LAK cell" precursor large granular lymphocytes in association with celiac disease.

We have investigated a case of lymphoproliferative disease of large granular lymphocytes (LDGL) occurring in association with celiac disease, anemia, neutropenia, and carcinomas of the endometrium, breast, and skin. The large granular lymphocyte (LGL) proliferation was monoclonal, T cell in origin, with T cell receptor beta-chain gene rearrangement, and a CD3+, CD8+, CD16+/- phenotype. In spite of the high frequency of LGL, natural killer (NK) cell activity was absent. Stimulation with interleukin-2 in vitro, however, resulted in high lymphokine-activated killer (LAK) cell activity against NK-resistant targets. The T-cell nature of the LAK precursor cells is in contrast to the majority seen in normal peripheral blood. Therapeutic trials of cyclosporin A, low-dose cyclophosphamide, and levamisole were unsuccessful in reducing transfusion requirements. This case is unique in the association of LDGL with celiac disease. It is also unique in that the patient had been followed for several years prior to the onset of the LDGL. The case extends the list of lymphoproliferative disorders documented to be associated with celiac disease and, conversely, adds to our knowledge of lymphoproliferative disorder of LGL and its "dysimmune" manifestations.

Celiac Disease↗
PubMed1993

Ductular proliferation and hepatic secretory function in experimental fascioliasis.

Proliferation of bile duct-like epithelial cells is a common feature of extrahepatic biliary obstruction and it is also present in other forms of liver disease. Experimental infestation with Fasciola hepatica induces hyperplasia of ductular cells together with different functional alterations, such as hypercholeresis, in the rat. We have investigated the contribution of ductular biliary secretion to the hypercholeretic phenomenon in rats with experimental fascioliasis. Infestation was induced by oral administration of 20 metacercariae of F. hepatica. Twelve weeks later, histological study of the liver showed a hyperplastic reaction with proliferation of bile duct-like structures. Basal bile flow in infested animals was significantly higher than that of control animals (+17%), while biliary secretion of bile acids did not significantly differ between both groups. Bile flow increase was associated in parasitized animals with a significantly lower [14C]mannitol bile:plasma ratio (-23%). Intravenous secretin administration (0.3 CU/100 g body wt min) induced a significant increase in the biliary concentration of bicarbonate (+21%) and an enhancement of bile flow (+21%) only in the animals with ductular proliferation. Taurocholate infusion (0.5 nmol/100 g body wt min) produced a similar bile flow increase both in control rats and in rats with proliferated biliary ductules. These results indicate that proliferated bile ductules and ducts spontaneously secrete bile in response to infestation by F. hepatica and that secretin-stimulated bile flow originates at the proliferated biliary structures.

Animals↗
PubMed1993

A bifunctional protein in the folate biosynthetic pathway of Streptococcus pneumoniae with dihydroneopterin aldolase and hydroxymethyldihydropterin pyrophosphokinase activities.

A protein encoded by sulD, one of four genes in a previously cloned folate biosynthetic operon of Streptococcus pneumoniae, had been shown to harbor 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase activity. This SulD protein was purified and shown now to harbor also dihydroneopterin aldolase activity. The bifunctional protein therefore catalyzes two successive steps in folate biosynthesis. The aldolase activity can be ascribed to the N-terminal domain of the SulD polypeptide, and the pyrophosphokinase activity can be ascribed to the C-terminal domain. Homologs of the dihydroneopterin aldolase domain were identified in other species, in one of which the domain was encoded as a separate polypeptide. The native SulD protein is a trimer or tetramer of a 31-kDa subunit, and it dissociated reversibly after purification. Dihydroneopterin aldolase activity required the multimeric protein, whereas pyrophosphokinase was expressed by the monomeric form. With purified SulD, the amount of 6-hydroxymethyl-7,8-dihydropterin product formed by the aldolase was proportional to the fourth power of the enzyme concentration, as expected for a reversibly dissociating tetramer. By identifying the gene encoding dihydroneopterin aldolase, this work extends our understanding of the molecular basis of the folate biosynthetic system common to many organisms.

Aldehyde-Lyases↗
PubMed1993

Phase II study of weekly edatrexate as first-line chemotherapy for metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study to assess the efficacy and toxicity of edatrexate, a folate antagonist, in 35 patients with metastatic breast cancer. PATIENTS AND METHODS: The planned dose of edatrexate was 80 mg/m2/wk administered intravenously as first-line therapy. Prior adjuvant chemotherapy was allowed provided at least 12 months had elapsed from the completion of treatment to the development of recurrence. RESULTS: Mucositis was the dose-limiting toxicity in 34 assessable patients, resulting in a mean delivered dose-intensity of 57 mg/m2/wk. Other toxicities included myelosuppression, rash, pneumonitis, and increased AST. Side effects were generally mild to moderate. The complete plus partial remission rate (13 patients; 41%) was impressive. CONCLUSION: Edatrexate is an active agent against metastatic breast cancer, with acceptable toxicity. A lower than planned delivered dose-intensity was mainly due to mucositis.

Adult↗
PubMed1993

[The fundamental basis and obstetrical applications of mifepristone or RU-486 (voluntary interrupted pregnancies excluded)].

RU 486 is an anti-progesterone steroid used in obstetrics to achieve maturation of the cervix before an endouterine procedure in late abortions during the first 3 months, in therapeutic pregnancy termination during months 3-6 or 6-9 and in expelling fetuses which have died in utero. RU 486 has also been proposed for use in inducing or facilitating labor at term.

Cervix Uteri↗
PubMed1993

Clinical theophylline toxicity: acute and chronic.

Reliable methods for measuring serum theophylline levels have provided the clinician with a range of serum theophylline concentrations to maximize therapeutic results while minimizing potential adverse effects. Although serum theophylline levels are often quoted for diagnosing theophylline toxicity, intolerance of this agent is closely associated with clinical features that are more important than an absolute serum value. This report contrasts the two most common settings of theophylline toxicity and presents an approach to the treatment of each type.

Adult↗