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Biomedical subjects

S Moreno

Publications and source records attributed to S Moreno.

At least 19 recordsLinked to original sources

Fever of uncertain origin in patients infected with the human immunodeficiency virus.

To assess the frequency and etiology of fever of uncertain origin (FUO) in patients infected with the human immunodeficiency virus (HIV) and to evaluate the yield of diagnostic procedures used in their evaluation, we reviewed the clinical charts of all patients admitted to an AIDS unit during a 15-month period. FUO was defined by the endurance of a fever (temperature, > 38.2 degrees C) for at least 4 weeks before admission and the uncertainty of diagnosis after 3 days, despite appropriate investigation. Of 580 patients evaluated, 50 (8.2%) had FUO. Patients with FUO were at advanced stages of HIV infection (median CD4+ cell count, 71/mm3), and a vast majority (84%) had previously diagnosed AIDS. A cause of the fever was identified for 44 patients (88%), and infections accounted for 82% of all cases. Tuberculosis (42%), visceral leishmaniasis (14%), and disseminated Mycobacterium avium complex infection (14%) were the most frequent diagnoses. Examination of lymph node aspirates, bone marrow biopsy, and culture of clinical specimens for mycobacteria were the procedures with the highest diagnostic yield. Among 6 patients with fever of no identified etiology, 4 died while febrile, and fever was self-limited in the other 2 patients. FUO is common among patients with advanced HIV infection. Since a cause, usually infection, can be identified in most patients, long-lasting fever should not be attributed to HIV itself.

Adult

Infections caused by erythromycin-resistant Streptococcus pneumoniae: incidence, risk factors, and response to therapy in a prospective study.

To evaluate the incidence and the significance of resistance to erythromycin among clinical isolates of Streptococcus pneumoniae, we identified and prospectively followed all hospitalized patients in a 27-month period who had the organism isolated from any clinical sample. Patients who had an infection caused by pneumococci resistant to erythromycin (minimum inhibitory concentration, > 1 microgram/mL) were compared to those with infections caused by erythromycin-susceptible organisms. The incidence of erythromycin resistance among pneumococci doubled over the study period (from 7.6% in 1988 to 15.2% in 1992). Most strains (94%) showed resistance to multiple antibiotics, including other macrolides. By multivariate analysis, an age of < 5 years and nosocomial acquisition of the infection were independent risk factors for erythromycin resistance. Among patients with pneumococcal pneumonia caused by erythromycin-resistant organisms, 9 patients treated with third-generation cephalosporins were cured, while therapy with erythromycin failed for 2 of the 6 patients to whom it was administered. The rapid and significant increase of erythromycin resistance among clinical isolates of S. pneumoniae points to the need for routine surveillance of pneumococcal resistance.

Adolescent

Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus.

Mupirocin is a topically applied drug that is very active in the eradication of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, studies designed to compare mupirocin treatment with other antimicrobial regimens are lacking. We therefore conducted an open, prospective, randomized, controlled trial to compare the efficacy and safety of mupirocin versus those of oral co-trimoxazole plus topical fusidic acid (both regimens with a clorhexidine scrub bath) for the eradication of MRSA from nasal and extranasal carriers of MRSA. The eradication rates with mupirocin and co-trimoxazole plus fusidic acid at 2, 7, 14, 21, 28, and 90 days were 93 and of 93, 100 and 100, 97 and 94, 100 and 92, 96 and 95, and 78 and 71%, respectively, for nasal carriage. At 7, 14, and 28 days the eradication rates for extranasal carriage by the two regimens were 23 and 74, 83 and 76, and 45 and 69%, respectively. The efficacies and safety of both regimens were similar. The MRSA isolates were not resistant to the study drugs either at the baseline or at follow-up. These results suggest that mupirocin and co-trimoxazole plus fusidic acid, both used in conjunction with a chlorhexidine soap bath, are equally effective and safe for the eradication of MRSA from nasal and extranasal MRSA carriers. Mupirocin was easier to use but was more expensive.

Administration, Oral

Interaction of cdc2 and rum1 regulates Start and S-phase in fission yeast.

The p34cdc2 kinase is essential for progression past Start in the G1 phase of the fission yeast cell cycle, and also acts in G2 to promote mitotic entry. Whilst very little is known about the G1 function of cdc2, the rum1 gene has recently been shown to encode an important regulator of Start in fission yeast, and a model for rum1 function suggests that it inhibits p34cdc2 activity. Here we present genetic data suggesting that rum1 maintains p34cdc2 in a pre-Start G1 form, inhibiting its activity until the cell achieves the critical mass required for Start, and find that in the absence of rum1 p34cdc2 has increased Start activity in vivo. It is also known that mutation of cdc2, or overexpression of rum1, can disrupt the dependency of S-phase upon mitosis, resulting in an extra round of S-phase in the absence of mitosis. We show that cdc2 and rum1 interact in this process, and describe dominant cdc2 mutants causing multiple rounds of S-phase in the absence of mitosis. We suggest that interaction of rum1 and cdc2 regulates Start, and this interaction is important for the regulation of S-phase within the cell cycle.

CDC2 Protein Kinase

MR imaging and CT of central nervous system tuberculosis in the patient with AIDS.

CNS TB represents a disease that complicates AIDS with an increasing incidence in endemic areas as well as in developed countries in those patients who have some risk factors such as intravenous drug abuse. Although TB infection of the CNS in AIDS patients may follow a rapidly progressive course, the imaging findings otherwise are similar to those of the nonimmunosuppressed population. Meningeal enhancement, hydrocephalus, parenchymal granulomata, and infarcts are seen frequently and are often observed in combination with one another. Nevertheless, the differential diagnosis in AIDS patients must include other opportunistic infections and primary or metastatic lymphoma of the CNS. Spinal TB usually is seen in the form of epidural abscess secondary to tuberculous spondylitis, although it may be seen in isolation of spinal column involvement. The differential diagnosis includes spinal lymphoma or pyogenic abscess formation. Radiculomyelitis or isolated spinal cord tuberculomata are much less frequently observed and can be suspected on imaging only if there is concomitant evidence of the classic findings of intracranial TB.

AIDS-Related Opportunistic Infections

[Fever evolution after treatment in patients with tuberculosis and HIV infection].

OBJECTIVES: To compare the fever course after starting therapy in patients diagnosed of active tuberculosis with and without HIV infection and evaluate the usefulness of empiric antituberculous therapy in diagnosing the disease. METHODS: Review of clinical records from all patients meeting the following criteria for three years: recovery of Mycobacterium tuberculosis from any clinical sample, knowledge of serological status to HIV, initial therapy of tuberculosis, absence of ther causes of fever identified, and not being treated with drugs which potentially could interfere with the course of fever during their hospital stay. RESULTS: At admission HIV-positive patients with tuberculosis were afebrile in a significantly lower proportion than HIV-negative patients (17% vs. 54%, respectively; p < 0.001). After initiating antituberculous therapy, the median time to fever resolution was similar in both HIV-positive and HIV-negative patients (6 and 4 days, respectively). After two weeks of therapy, 25% of HIV-positive patients and 23% HIV-negative patients still had fever. No factor was identified which could predict the delay in resolution of fever. CONCLUSIONS: The course of fever was similar in both HIV-positive and HIV-negative patients after initiating antituberculous therapy. This empirical therapy may be useful in diagnosing tuberculosis, as fever resolved in the first two weeks of therapy in most patients.

AIDS-Related Opportunistic Infections

[Tuberculosis presenting as diffuse pulmonary infiltrates in AIDS patients: diagnostic performance of clinical samples].

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, tuberculosis is frequently presented with diffuse pulmonary infiltrates which are indistinguishable from those caused by other respiratory pathogens. It is therefore useful to know the diagnostic performance of different clinical samples. METHODS: We have retrospectively analyzed the clinical histories of 56 patients seen over a 3-year period. All the patients had HIV infection, Mycobacterium tuberculosis isolated in at least one clinical sample and presented with diffuse bilateral infiltrates in thorax radiography. The results of all the clinical samples submitted to the microbiology laboratory. RESULTS: The highest performance in both stainings and cultures were obtained from the biopsy (or aspirate) of adenopathies (93 and 100%, respectively), sputum (57 and 88%) and urine (31 and 64%). A lower than expected sensitivity was obtained in the fibrobronchoscopy samples (bronchoalveolar lavage and transbronchial biopsy). The staining had low sensitivity for predicting positive cultures in all the samples except in the adenopathies. Visualization of granulomas in transbronchial biopsies and bone marrow was more sensitive for diagnosis than the demonstration of resistant acid-alcohol bacilli in the same samples. Globally, rapid diagnosis was obtained in 43 patients (76%). The remaining 13 (24%) patients were not diagnosed until the culture results had been received despite the adequate use of diagnostic procedures. CONCLUSIONS: These findings support the use of empiric treatment when tuberculosis is suspected despite initial negativity of the microbiologic and pathologic examinations following the discarding of other potential causes.

AIDS-Related Opportunistic Infections

Regulation of the cell cycle timing of Start in fission yeast by the rum1+ gene.

We have identified the rum1+ gene as a new regulator of the G1-phase of the fission yeast cell cycle. rum1+ determines the cell cycle timing of Start, by maintaining cells in a pre-Start state until they have attained a minimal critical mass. Cells lacking rum1+ are unable to arrest in pre-Start G1 in response to nitrogen starvation and are subsequently sterile. In addition, rum1+ prevents entry into mitosis from pre-Start G1, as shown by the fact that cdc10 mutants in the absence of rum1+ undergo lethal mitosis without entering S-phase.

Cell Cycle

Molecular genetics of the glutamine synthetases in Rhizobium species.

Soil bacteria of the genus Rhizobium and Bradyrhizobium establish symbiotic interactions with leguminous plants that result in the formation of specialized structures, the nodules, in which the bacteria differentiate into bacteroids and fix nitrogen. Rhizobial glutamine synthetase (GS) activity is very low in the nodule. The ammonia produced by the bacteroids is exported to the plant cell, where it is assimilated by the GS from the plant, whereas in the free-living state, Rhizobium and Bradyrhizobium species assimilate ammonia for growth. Another characteristic of these species is that they possess two glutamine synthetase isozymes, known as GSI and GSII. A third glutamine synthetase isozyme, called GSIII, has been found in R. meliloti and R. etli.

Amino Acid Sequence

Immobilization of coypus (Myocastor coypus) with ketamine hydrochloride and xylazine hydrochloride.

A combination of 100 mg/ml of ketamine hydrochloride (Ket) and 20 mg/ml of xylazine hydrochloride (Xyl) was used to immobilize coypus (Myocastor coypus). Eight mature coypus (four males and four females) were injected intramuscularly with doses ranging from 2.33 to 6.25 mg/kg of KET and 0.25 to 0.86 mg/kg of Xyl. The mean (+/- SE) time for induction, arousal, and recovery were 7.3 +/- 2 min, 23.5 +/- 0.3 min and 46 +/- 2.5 min, respectively. The mean +/- SE doses injected were 4.07 +/- 0.52 mg/kg Ket (range, 2.33 to 6.25 mg/kg) and 0.5 +/- 0.08 mg/kg Xyl (range, 0.25 to 0.86 mg/kg). No adverse responses were observed in any of the animals treated.

Animals

Effects of Di-(2-ethylhexyl)phthalate on peroxisomes of liver, kidney and brain of lactating rats and their pups.

Di-(2-ethylhexyl)phthalate administered to adult lactating rats, from delivery to weaning, induces modifications of the peroxisomal enzymatic pattern in the liver, kidney and brain of both dams and pups. These modifications are age- and organ-dependent. Biochemical analysis shows that: 1) catalase specific activity is two-fold increased in the liver of both adult and newborn animals, in the kidney of newborns and in the brain of adults. 2)D-amino acid oxidase doubles in all newborn organs and in adult brain; it increases, although to a lesser extent, also in adult kidney, while it is half-reduced in adult liver. 3) Dihydroxyacetone phosphate acyl transferase only doubles in newborn liver, remaining fairly unchanged in all the other tested tissues. 4) Palmitoyl-CoA oxidase is greatly induced in the liver of both dams and litters, doubled in the kidneys and slightly increased or not at all in the brain of pups and mothers, respectively. The effect of the drug on enzyme activities is reversible, with different time courses depending on the considered enzyme and organ. Western blottings confirm the biochemical data. Electron microscopy shows proliferated peroxisomes in the liver and kidney of treated animals but not in the brain, where high catalase-like immunoreactivity is observed in the cytosol of neurons. Taken together, our data demonstrate that the response of peroxisomal enzymes to DEHP treatment is age- as well as tissue-dependent and specific for each enzyme studied.

Acyltransferases

Isobutylmethylxanthine and other classical cyclic nucleotide phosphodiesterase inhibitors affect cAMP-dependent protein kinase activity.

The effect of 17 inhibitors of cyclic nucleotide phosphodiesterases (PDEs) was assayed on cAMP binding activity of Mucor rouxii protein kinase A (PKA), on PKA activity in the absence of cAMP and on free catalytic subunit (C) activity. Isobutylmethylxanthine (IBMX), SQ 20,009 and cilostamide, at 0.2 mM, behaved as partial agonists of cAMP since they inhibited binding of 0.15 microM [3H]cAMP to the regulatory subunit (R), stimulated slightly PKA activity in the absence of cAMP and did not modify C activity. Amrinone at 0.2 mM inhibited C activity competitively towards ATP. These four compounds displayed the same effects when assayed on eukaryotic protein kinase A types I (PKI) and II (PKII). The combined effect of IBMX and cAMP was analysed on Mucor PKA. Under dissociating conditions (+ 0.5 M NaCl) IBMX antagonized activation by low concentrations of cAMP, while in the absence of NaCl, IBMX potentiated the stimulating activity of cAMP.

1-Methyl-3-isobutylxanthine

Tuberculous meningitis in patients infected with the human immunodeficiency virus.

BACKGROUND AND METHODS: Tuberculosis is a frequent complication of human immunodeficiency virus (HIV) infection. We describe the clinical manifestations and outcomes of tuberculous meningitis in patients with HIV infection, and compare them with those in non-HIV-infected patients. We reviewed the records from 1985 through 1990 at two large referral hospitals in Madrid for patients who had Mycobacterium tuberculosis isolated from cerebrospinal fluid. RESULTS: Of 2205 patients with tuberculosis, 455 (21 percent) also had HIV infection, of whom 45 had M. tuberculosis isolated from the cerebrospinal fluid. Of the 37 HIV-infected patients with tuberculous meningitis for whom records were available, 24 (65 percent) had clinical or radiologic evidence of extrameningeal tuberculosis at the time of admission. In 18 of 26 patients (69 percent), a CT scan of the head was abnormal. In most patients, analysis of cerebrospinal fluid showed pleocytosis (median white-cell count, 0.234 x 10(9) per liter) and hypoglycorrhachia (median glucose level, 1.3 mmol per liter), but in 43 percent (15 of 35), the level of protein in cerebrospinal fluid was normal. In four patients with HIV infection, tuberculosis was only discovered after their deaths. Of the 33 patients who received antituberculous treatment, 7 died (in-hospital mortality, 21 percent). Illness lasting more than 14 days before admission and a CD4+ cell count of less than 0.2 x 10(9) per liter (200 per cubic millimeter) were associated with a poor prognosis. Comparison with tuberculous meningitis in patients without HIV infection showed that the presentation, clinical manifestations, cerebrospinal fluid findings, and mortality were generally similar in the two groups. However, of the 1750 patients without HIV infection, only 2 percent (38 patients) had tuberculous meningitis, as compared with 10 percent of the HIV-infected patients (P less than 0.001). CONCLUSIONS: HIV-infected patients with tuberculosis are at increased risk for meningitis, but infection with HIV does not appear to change the clinical manifestations or the outcome of tuberculous meningitis.

Acquired Immunodeficiency Syndrome

Pneumococcal pneumonia in adult hospitalized patients infected with the human immunodeficiency virus.

PURPOSE: To determine the attack rate; clinical, radiologic, and laboratory characteristics; and outcome of pneumococcal pneumonia in patients infected with the human immunodeficiency virus (HIV) and to compare these characteristics with those of pneumococcal pneumonia in the general population. PATIENTS AND METHODS: This is a retrospective (13-month), prospective (14-month) study. All adult hospitalized patients with pulmonary infiltrates and isolation of Streptococcus pneumoniae in blood, pleural fluid, transtracheal aspirate, or respiratory secretions obtained by plugged telescoped catheter (counts greater than 10(3) colony-forming units per milliliter) are included. MAIN RESULTS: We identified 22 HIV-infected patients and 84 HIV-seronegative patients with pneumococcal pneumonia (76% and 56%, respectively, were bacteremic). The estimated attack rate was 5.9 per 1000 for HIV-infected patients and 0.31 per 1000 for HIV-seronegative patients. Pneumococcal pneumonia was the first manifestation of HIV infection in 48% of cases. Seventy-two percent of patients younger than 40 years of age with pneumococcal pneumonia were HIV infected. No predisposing factors for pneumococcal pneumonia were identified in 76% and 2% of HIV seropositive and seronegative patients, respectively. Clinical and radiologic presentation was similar in the two populations. Of all S pneumoniae isolates, 35% were resistant to penicillin and 10% to erythromycin, without differences in the two groups. Prognosis was good, with only one infection-related death in the HIV-infected group (10 patients died in the other group). No relapses were documented in HIV-infected patients. CONCLUSION: The HIV-infected patient is at increased risk for pneumococcal pneumonia and bacteremia. Patients younger than 40 years of age who present with pneumococcal pneumonia should be considered for HIV testing, since it may be the first manifestation of HIV infection. Specific antimicrobial therapy is curative in the majority of HIV-infected patients.

AIDS Serodiagnosis

Autophosphorylation of Mucor rouxii cAMP-dependent protein kinase and its role in holoenzyme activation.

Two phosphoproteins of 53,000 and 63,000 mol. wt detected in partially purified preparations of Mucor rouxii cAMP-dependent protein kinase submitted to phosphorylation conditions with [gamma-32P]ATP are demonstrated to be the result of the autophosphorylation of its regulatory subunit, according to the following criteria: (1) linearity of phosphate incorporation with enzyme sample; (2) independence of phosphate incorporation on temperature; (3) correlation of the phosphoproteins with enzymatic activity in a DEAE-Sepharose chromatography; (4) specific elution of the phosphorylated proteins from cAMP-agarose; (5) phosphorylation of the purified regulatory subunit. Antibodies specific against Mucor regulatory subunit detected an intact subunit of 72,000 mol. wt in crude extracts. Autophosphorylation of the fungal protein kinase A promotes activation of the holoenzyme by cAMP since: (1) under conditions of partial activation, increase of activity is observed when using the phosphoform of the enzyme; (2) release of free catalytic subunit from cAMP-agarose is enhanced when the holoenzyme is previously phosphorylated.

Adenosine Triphosphate

Phenotype of a Rhizobium leguminosarum ntrC mutant.

A Tn5 insertion mutant, strain CFN2012, of Rhizobium leguminosarum biovar phaseoli devoid of glutamine synthetase II (GSII) activity was analysed. It was shown to contain Tn5 within an 11-kb BamHI DNA fragment, which was isolated (pSM261) from the wild-type strain and, when introduced into strain CFN2012, was shown to complement the absence of GSII activity. The DNA sequence of the corresponding region from the wild-type allele revealed the presence of an ntrC regulatory gene, and restriction analysis indicated that the mutant allele carried the Tn5 insertion within it. Further analysis of strain CFN2012 indicated that this mutant has reduced levels of the PII regulatory protein and that, in contrast to ntrC mutants of other Rhizobiaceae, it grows on nitrate as the sole nitrogen source.

Bacterial Proteins

Group B Streptococcus: a cause of urinary tract infection in nonpregnant adults.

Group B Streptococcus (GBS) is a well-known cause of infection in the perinatal and puerperal periods, but its role as a urinary tract pathogen of adults in nonobstetric situations has not yet been defined. We carried out a prospective 19-month study of all nonpregnant adult patients with significant GBS bacteriuria. This microorganism accounted for 2% of positive urine cultures. Our series included 60 patients, 85% of whom were women and 95% of whom had at least one underlying condition. Urinary tract abnormalities (60%) and chronic renal failure (27%) were among the most frequent underlying problems. The infection was community acquired in 65% of cases. Clinical manifestations were related equally to the upper and the lower urinary tract (37% and 38% of cases, respectively). The clinical outcome was poor in 18% of episodes despite treatment. All isolates were sensitive to all antibiotics tested except gentamicin. We conclude that GBS is a significant urinary pathogen in nonpregnant adults and that its presence signals a need for screening for urinary tract abnormalities.

Adult