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Biomedical subjects

M Fernandez

Publications and source records attributed to M Fernandez.

At least 73 records · Page 4Linked to original sources
PubMed2000

Discitis and vertebral osteomyelitis in children: an 18-year review.

BACKGROUND: Discitis and vertebral osteomyelitis are uncommon entities, and diagnosis often is confounded by their similar clinical presentation, because characteristic radiographic findings are not evident until late in the course of illness. OBJECTIVE: To compare the age distribution, clinical manifestations, and radiographic findings, especially magnetic resonance imaging (MRI), in children with discitis or vertebral osteomyelitis. METHODS: A retrospective review of 57 children with a discharge diagnosis of discitis or vertebral osteomyelitis hospitalized from January 1980 through December 1998. RESULTS: Fifty patients met inclusion criteria: 36 with discitis and 14 with vertebral osteomyelitis. The mean age at presentation was younger for children with discitis than for those with vertebral osteomyelitis (2.8 vs 7.5 years of age) and the duration of symptoms longer for children with vertebral osteomyelitis than for those with discitis (33 vs 22 days). The initial symptom for both groups of children was refusal to walk, limp, or back pain, but children with osteomyelitis more often were febrile (79% vs 28%) and ill-appearing than those with discitis. Thirty-three patients with discitis had radiographs of the spine; 25 (76%) had abnormalities that were diagnostic. Ten discitis patients had MRI; 9 (90%) had abnormalities consistent with this diagnosis. Thirteen children with vertebral osteomyelitis had radiographs of the spine, but in only 7 (54%) were these abnormal. However, 11 had MRIs, and in each the diagnosis of vertebral osteomyelitis was established. CONCLUSION: This comparative study suggests that age and clinical presentation distinguish most patients with discitis from those with vertebral osteomyelitis. Although radiographs of the spine usually are sufficient to establish the diagnosis of discitis, MRI is the diagnostic study of choice for pediatric patients with suspected vertebral osteomyelitis.

Adolescent↗
PubMed2000

Laparoscopic ultrasound enhances diagnostic laparoscopy in the staging of intra-abdominal neoplasms.

Routine laparoscopy and laparoscopic ultrasound (LUS) for staging intra-abdominal malignancies remains controversial. Thus, we undertook a prospective study to assess the value of preoperative laparoscopy with LUS for patients with intra-abdominal tumors judged resectable by preoperative studies. Laparoscopy was successfully performed in 76 of 77 patients, and 60 underwent LUS. Of 33 patients with presumed pancreatic cancer, laparoscopic findings changed the operative management of 11 patients, and LUS altered the management of an additional 6 patients. Laparotomy was avoided in 9 patients (27%). Among 14 patients with hepatobiliary tumors, laparotomy was avoided in 9 patients in whom laparoscopy and/or LUS revealed either benign or advanced disease. Operative management was altered in 4 of 18 patients with gastric or esophageal cancer by laparoscopic findings. LUS did not add to the management of these patients. Of 12 patients with presumed intra-abdominal lymphoma, 9 were diagnosed with lymphoma and 3 with benign disease, without laparotomy in all but 1 case. Laparoscopy and LUS are valuable tools for evaluating the resectability of pancreatic and hepatobiliary tumors. Laparoscopy, and to a lesser degree LUS, greatly facilitates diagnosing patients with intra-abdominal lymphomas and spares an occasional patient with esophagogastric carcinoma from undergoing laparotomy.

Carcinoma↗
PubMed1999

Cross-resistance of dideoxycytidine-resistant cell lines to azidothymidine.

2',3'-Dideoxycytidine (ddC) and azidothymidine (AZT) inhibit HIV-1 replication and currently are used in AIDS therapy. Long-term use of the drugs is associated with the selection of drug-resistant HIV strains, thus limiting their effectiveness. Another mechanism, associated with their altered metabolism in host cells, also can cause "cellular" drug resistance. Human lymphocytic H9 cell lines (H9-ddC0.5w and H9-ddC5.0w) selected for ddC resistance by exposure to 0.5 and 5.0 microM ddC were found to be cross-resistant to AZT. Compared with controls, the thymidine kinase (TK) activities in H9-ddC0.5w and H9-ddC5.0w cells were 56.7 and 51.4% (with thymidine as a substrate) and 50.3 and 42% (with AZT as a substrate). Consequently the cellular incorporation of AZT and thymidine (24-hr incubation) also was reduced to 51.3 and 70.0% in H9-ddC0.5w cells and to 12.1 and 17.3% in H9-ddC5.0w cells. A 3-hr incubation with 25 microM AZT and ddC decreased their cellular incorporation to 50.5 and 76.15% in H9-ddC0.5w cells and to 12.95 and 47.8% in H9-ddC5.0w cells compared with H9 cells. Thus, the change in AZT accumulation did not correlate exactly with the decrease in TK activity and far exceeded the effect on ddC accumulation. Evidence is presented that ddC, in addition to deoxycytidine kinase, affected TK1 activity. The involvement of multidrug resistance proteins in the mechanism of the resistance was ruled out by the failure of trifluoperazine and verapamil to alter cellular accumulations of AZT, ddC, daunorubicin, and rhodamine-123. Development of cellular ddC and AZT cross-resistance may affect the therapeutic efficacy of these antiviral agents.

Anti-HIV Agents↗
PubMed1999

Collateral resistance of a dideoxycytidine-resistant cell line to 5-fluoro-2'-deoxyuridine.

Exposure of a human lymphocytic cell line, H9 cells, to 0.5 microM and 5.0 microM dideoxycytidine (ddC) resulted in isolation of ddC-resistant H9-ddC0.5w and H9-ddC5.0w cell lines. In addition, these cell lines were also resistant to azidothymidine and had reduced deoxycytidine kinase and thymidine kinase activities. We now show that these cell lines are 4-fold and 2000-fold collaterally resistant to 5-fluoro-2'-deoxyuridine (FdUR), respectively, but not to 5-fluorouracil (FU). Biochemical evaluations show that, compared to the parental cells, the FdUR phosphorylation was reduced to 36.3% and 9.2% and the FdUMP levels were decreased to 48.1% and 1.2% in these cell lines. Taken together, the data suggest that ddC, an antiviral agent, is capable of inducing resistance to FdUR-a drug that is not its analog and which has a different metabolism, target site, and mechanism of action.

Antimetabolites, Antineoplastic↗
PubMed1999

Development of viral vectors for gene therapy of beta-chain hemoglobinopathies: optimization of a gamma-globin gene expression cassette.

Progress toward gene therapy of beta-chain hemoglobinopathies has been limited in part by poor expression of globin genes in virus vectors. To derive an optimal expression cassette, we systematically analyzed the sequence requirements and relative strengths of the Agamma- and beta-globin promoters, the activities of various erythroid-specific enhancers, and the importance of flanking and intronic sequences. Expression was analyzed by RNase protection after stable plasmid transfection of the murine erythroleukemia cell line, MEL585. Promoter truncation studies showed that the Agamma-globin promoter could be deleted to -159 without affecting expression, while deleting the beta-globin promoter to -127 actually increased expression compared with longer fragments. Expression from the optimal beta-globin gene promoter was consistently higher than that from the optimal Agamma-globin promoter, regardless of the enhancer used. Enhancers tested included a 2.5-kb composite of the beta-globin locus control region (termed a muLCR), a combination of the HS2 and HS3 core elements of the LCR, and the HS-40 core element of the alpha-globin locus. All three enhancers increased expression from the beta-globin gene to roughly the same extent, while the HS-40 element was notably less effective with the Agamma-globin gene. However, the HS-40 element was able to efficiently enhance expression of a Agamma-globin gene linked to the beta-globin promoter. Inclusion of extended 3' sequences from either the beta-globin or the Agamma-globin genes had no significant effect on expression. A 714-bp internal deletion of Agamma-globin intron 2 unexpectedly increased expression more than twofold. With the combination of a -127 beta-globin promoter, an Agamma-globin gene with the internal deletion of intron 2, and a single copy of the HS-40 enhancer, gamma-globin expression averaged 166% of murine alpha-globin mRNA per copy in six pools and 105% in nine clones. When placed in a retrovirus vector, this cassette was also expressed at high levels in MEL585 cells (averaging 75% of murine alpha-globin mRNA per copy) without reducing virus titers. However, recombined provirus or aberrant splicing was observed in 5 of 12 clones, indicating a significant degree of genetic instability. Taken together, these data demonstrate the development of an optimal expression cassette for gamma-globin capable of efficient expression in a retrovirus vector and form the basis for further refinement of vectors containing this cassette.

Anemia, Sickle Cell↗
PubMed1999

Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats.

Heme oxygenase (HO) catalyzes the conversion of heme into biliverdin, iron, and carbon monoxide (CO). Two isoforms of HO have been identified: the inducible HO-1 and the constitutive HO-2. CO, like nitric oxide, is an endogenous vasodilator that could contribute to modulation of systemic and local vascular tone. The aim of the present study was to determine the expression of HO isoforms in liver cells and splanchnic organs from portal hypertensive (PH) and sham-operated (SO) rats. Liver cells (hepatocytes, Kupffer and stellate cells), and splanchnic organs (liver, mesentery, intestine, colon, and spleen) were isolated from PH and SO rats. Expression of HO mRNA and protein was assessed by reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. In SO rats, HO-1 mRNA expression was only detected in spleen. In contrast, in PH rats, HO-1 mRNA was expressed in hepatocytes, Kupffer cells, and in all the splanchnic organs studied. Moreover, levels of HO-1 protein in splanchnic organs were significantly higher in PH rats than in SO animals. In addition, HO-2 expression was observed in all liver cell types and splanchnic organs studied from both PH and SO rats. These results indicate that HO-2 is expressed in parenchymal and nonparenchymal liver cells, as well as splanchnic organs, of both PH and SO rats. In addition, HO-1 is up-regulated in hepatocytes and splanchnic organs of PH rats, compared with SO animals, suggesting a possible pathophysiological role of HO-1 in chronic portal hypertension.

Animals↗
PubMed1999

Processes of liquefaction/solubilization of Spanish coals by microorganisms

Several fundamental aspects of microbial coal liquefaction/solubilization were studied. The liquefied/solubilized products from coal by microorganisms were analysed. The liquid products analysed by IR titration and UV/visible spectrometry showed some alterations with regard to the original coal. Humic acids extracted from the liquefied lignite showed a reduction in the average molecular weight and a increase in the condensation index, probably due to depolymerization caused by microorganisms. The mechanisms implicated in coal biosolubilization by two fungal strains, M2 (Trichoderma sp.) and M4 (Penicillium sp.) were also studied. Extracellular peroxidase, esterase and phenoloxidase enzymes appear to be involved in coal solubilization.

Journal Article↗
PubMed1999

Subjective ratings of odorants by women with chemical sensitivity.

The purpose of the present study was to investigate whether women with chemical sensitivity rated the intensity and pleasantness of three odorants [peppermint, vanilla, and propylene glycol (PG)] and odorless room air differently than women without chemical sensitivity. The ratings of the experimental group (women with self-reported chemical sensitivity and no history of sexual abuse) were compared to those of two control groups who did not report chemical sensitivity [sexually abused (SA) women and healthy women without sexual abuse history]. All subjects were exposed to odorants and odorless control stimuli once a week for 3 consecutive weeks. Our findings indicate that women with chemical sensitivity perceive odorants as neither more or less intense nor more or less pleasant than women without chemical sensitivity. Moreover, the control women without sexual abuse outperformed the women in the other two groups by correctly identifying the target bottle containing the odorant. These findings suggest that perception of odorants alone is unlikely to account for the symptoms associated with chemical sensitivity. These findings, along with those of Doty et al. (1988), support the notion that olfactory-sensory function does not differ between individuals with and without chemical sensitivity.

Adult↗
PubMed1998

Leishmania sp.: growth and survival are impaired by ion channel blockers.

In the present work we examined the effect of ion transport blockers on the growth and viability of Leishmania sp. and on the infection of macrophages by the parasite. 4-aminopyridine and glibenclamide block voltage-dependent and K+ ATP channels, respectively; amiloride is used to detect Na+ channels and Na+/H+ antiporters; and anthracene-9-carboxylic acid affects chloride channels. The EC50 for promastigote cultures of three strains of the Leishmania subgenus, namely, Leishmania (Leishmania) NR, Leishmania (Leishmania) amazonensis LTB0016, and Leishmania (Leishmania) major, at their stationary phase of growth, were, respectively, 39, 46, and 464 microM for 4-aminopyridine; 7, 0.8, and 10 microM for glibenclamide and 66, 170, and 10 microM for anthracene-9-carboxylic acid. The amiloride EC50 for NR was 264 microM and 10 microM for L. (L.) major, but was never reached for LTB0016. Higher concentrations of the drugs impaired the exponential growth of Leishmania promastigotes. These results suggest the susceptibility of Leishmania sp. to blockers associated with K+ and Cl- and to Na+ or Na+/H+ transport systems. Blockade of such systems might have impaired the survival of the parasites as promastigotes. In addition, it affected the persistence of parasites in host cells. Although the infection of the macrophage cell line J774 and peritoneal-exudate macrophages was not significantly decreased by concentrations of the drugs around the promastigotes' EC50, the survival of intracellular parasites decreased significantly in the presence of these drugs without affecting the viability of the macrophages. Some blockers consistently gave small EC50 and significantly decreased the infection process as well as the survival of intracellular parasites. Thus, elucidation of their mechanism of action in Leishmania is relevant, since they could represent a potential subject for the development of leishmanicidal drugs.

4-Aminopyridine↗
PubMed1998

Hospital attitudes: preliminary findings from donor action pilot projects.

PURPOSE: As part of the Donor Action collaboration (Eurotransplant Foundation, The Netherlands; Organización National de Transplantes, Spain; and The Partnership for Organ Donation, USA), a hospital survey was administered to gather baseline data on staff attitudes about organ donation and level of self-reported skills/confidence in performing a range of organ donation roles. METHODS: A standard survey instrument was administered in two hospitals in Spain, two in The Netherlands and one in the UK. In four hospitals the survey was administered to all ICU staff; in one hospital it was administered to a random sample of hospital staff. The instrument was created in English, and translated into Spanish and Dutch for the hospitals in each country. RESULTS: Data were analysed by country and showed consistently strong perceptions that organ donation saves lives (97%). Support for donation (95%) and willingness to donate one's own organs (82%) were high in all three country samples. Significant differences in belief were observed when respondents were asked whether they agreed that organ donation helps families with their grief. The UK respondents were more likely to agree (57%), with lower levels of agreement in Spain (47%) and The Netherlands (14%) (P < 0.0001). Average ratings of skills/confidence were highest for notifying the transplant coordinator (49%) and comforting the family (48%) with lower confidence reported regarding explaining brain death (34%), introducing organ donation (32%), and requesting organ donation (26%). Ratings varied widely across countries with UK respondents expressing the highest level of self-reported confidence, and Spanish respondents the lowest level. For example, 77% of UK respondents reported themselves skilled/confident explaining brain death, versus 47% of Dutch respondents and 11% of Spanish respondents (P < 0.0001). Similar results were seen regarding requesting organ donation: UK 53%; The Netherlands 30%; Spain 13% (P < 0.0001). CONCLUSIONS: There has been a lack of data about hospital staff attitudes and skills to allow for comparison across national systems, and to support the targeting of specific strategies to the needs within different countries. These results show the feasibility of collecting and comparing data across national systems. These pilot findings also suggest that there may be important differences in attitudes and self-perceived skills/confidence across countries. Work remains to correlate attitudes and self-perceived skills to actual performance. It is noteworthy that the sense of staff preparedness was lowest in Spain which has the highest donation rates. This may reflect the degree to which role specialization in donation has been successfully integrated into hospital practice. Expansion of the survey to additional hospitals will help to answer such questions.

Attitude↗
PubMed1998

Spatial and temporal trends of paraquat, diquat, and difenzoquat contamination in water from marsh areas of the valencian community (Spain)

The levels and distribution of diquat, paraquat, and difenzoquat were determined by solid phase extraction (SPE) and high-performance liquid chromatography (HPLC) in water samples from irrigation channels, rivers, and lagoons taken during 1 year from three different marsh areas of the Valencian community. These areas are representative of the typical Mediterranean coastal ecosystems. All three compounds were detected. Diquat was found most frequently at all the sampling sites. Although the spatial distribution of diquat and paraquat showed a maximum concentration near the fields where they were originally applied, their location fluctuated due to irregular large spill and/or loading. The herbicide concentration tended to be highest during the summer (June, July, and August) because these are the months with the least rainfall and highest evaporation rates, when weeds grow best and pesticides are needed more often. The average concentration found for diquat was 0.09 &mgr;g/L, with a maximum of 3.10 &mgr;g/L. The average concentration for paraquat was 0.01 &mgr;g/L, with a maximum of 3.95 &mgr;g/L. Samples that were below the method detection limit are included in the mean calculation as zero. Difenzoquat was only detected in one sample at a concentration of 1.75 &mgr;g/L.

Journal Article↗
PubMed1998

Phylogenetic relationships of the family Campulidae (Trematoda) based on 18S rRNA sequences.

Traditionally, the family Campulidae has been associated either with the family Fasciolidae, parasites of ruminants, or the Acanthocolpidae, parasites of fishes, based on morphological similarities. Since morphology does not seem to resolve clearly the problem of the relationships of campulids, we have used the sequences of the 18S rRNA gene of the campulids Zalophotrema hepaticum, Campula oblonga and Nasitrema globicephalae, the fasciolid Fasciola hepatica, the acanthocolpid Stephanostomum baccatum and the outgroup Schistosoma mansoni to infer a phylogeny. Maximum parsimony and neighbour-joining methods were applied. Both methods indicated that campulids are closer to acanthocolpids than fasciolids. In order to confirm this relationship, we generated a second phylogeny using all the partial sequences of the 18S published for trematodes: Lobatostoma manteri, Echinostoma caproni, Calicophoron calicophorum, Tetracerasta blepta, Gyliauchen sp. and Opistorchis viverrini, plus those mentioned above, and Dicrocoelium dendriticum. The aspidogastrean L. manteri was used as the outgroup. Results were identical to the first analysis. According to this and the most recent Digenean phylogeny, which considers campulids and acanthocolpids as sister groups, we suggest that a common origin for these 2 groups would imply a host-switching process. The life-cycle of acanthocolpids includes marine gastropods as first intermediate hosts, and fishes as second intermediate and definitive hosts. In this context, the hypothesis would be that trematodes whose cycle ended in fishes were able to switch to mammalian hosts.

Animals↗
PubMed1998

Reevaluation of antipyretics in children with enteric fever.

BACKGROUND: The Committee on Infectious Diseases of the American Academy of Pediatrics recommends withholding antipyretic administration to patients with enteric fever because of the risk of shock developing as a consequence. OBJECTIVE: To evaluate the effects of antipyretics on blood pressure in children with enteric fever. METHODS: A retrospective review of medical records of patients admitted to Texas Children's Hospital from January, 1977, to October, 1997, with a diagnosis of enteric fever. All febrile episodes were evaluated for the use of antipyretics and evidence of hypotension or cardiovascular decompensation associated with them. RESULTS: Twenty-nine patients with enteric fever were identified. Salmonella typhi caused 23 of these infections. Antipyretics were used in all but one patient. We did not find any association between the use of antipyretics and the development of hypotension. One patient developed shock and adult respiratory distress syndrome >36 h after start of antibiotic therapy and unrelated to fever or antipyretic use. Two patients had evidence of dehydration. No other complications occurred. CONCLUSIONS: We did not find any complications associated with the use of acetaminophen or ibuprofen in children with enteric fever. The effects of antipyretics in enteric fever should be further studied.

Acetaminophen↗
PubMed1998

Antimicrobial susceptibilities of group B streptococci isolated between 1992 and 1996 from patients with bacteremia or meningitis.

In vitro testing of 229 group B streptococcal isolates from a variety of patients with invasive infections indicated uniform penicillin G susceptibility. However, 17 (7.4%) isolates were resistant to erythromycin and 8 (3.4%) were resistant to clindamycin. These results support the continued use of penicillin G as the drug of choice for the treatment and prevention of group B streptococcal disease.

Adolescent↗