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Biomedical subjects

E Jimenez

Publications and source records attributed to E Jimenez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Insulin and blood pressure responses to changes in salt intake.

In this study we evaluated the role of insulin in hypertension and on salt sensitivity. The study was conducted in 47 consecutive patients attending the Center for the Detection and Treatment of Cardiovascular and Metabolic Risk factors. The relationships between fasting and post-glucose load insulin levels and the blood pressure (BP) responses to changes in salt intake, were investigated. No correlation was observed between fasting or 2-h post-load insulin levels and mean BP (MBP), systolic BP (SBP) or diastolic BP (DBP). The plasma concentrations of insulin were not significantly related to body mass index (BMI) (r2 = 0.05; P = 0.135). Neither fasting nor 2-h post-load insulin predicted the BP response to changes in salt intake. A reduction in salt intake from 316 +/- 13 to 26 PM 3 mmoles/day, produced similar BP lowering in subjects with fasting insulin >15 microU/ml and in subjects with normal fasting insulin levels (<15 microU/ml). In addition, no relationship was observed between the magnitude of the BP responses to salt and the levels of insulin, either fasting (r2 = 0.007; P = 0.86) or 2-h after a glucose load (r2 = 0.01; P = 0.213). A very strong association was found between body weight or BMI and MBP (r2 = 0.443; P< 0.0001). In conclusion, our results are against the view of a cause-effect relationship between insulin and BP levels. In addition, the insulin status of a patient does not predict (nor determines) his (her) vascular reactivity to changes in salt intake. Finally, our findings further support the existence of a strong and direct association between body weight and hypertension, and speak against a major role of insulin in the pathogenesis of hypertension associated with obesity.

Adult↗
PubMed2000

Successful airway control with the laryngeal mask in an infant with Beckwith-Wiedemann syndrome and hepatoblastoma for central line catheterization.

We present a case of an infant with severe macroglossia, hypoglycaemia and inguinal hernia associated with hepatoblastoma (Beckwith-Wiedemann syndrome) in which a laryngeal mask airway (LMA) was useful to secure the airway during central line insertion. Carbon dioxide monitoring through LMA proved effective to assess airway patency during positioning for central vein puncture. In this syndrome, where a potentially difficult airway may be encountered, LMA allowed adequate ventilation, avoiding the risk and inconvenience of tracheal intubation.

Beckwith-Wiedemann Syndrome↗
PubMed2000

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗
PubMed2000

Activities of sordarins in experimental models of candidiasis, aspergillosis, and pneumocystosis.

Sordarin derivatives represent a new class of antifungal agents that act as potent inhibitors of fungal protein synthesis and possess a broad spectrum of activity. The in vivo activity of GM193663 and GM237354 was studied in mouse models of disseminated candidiasis and aspergillosis and in a rat model of pneumocystosis. The pharmacokinetic behavior of both sordarin derivatives was studied in mice and rats. In all studies, compounds were administered by the subcutaneous route. After a subcutaneous dose of 50 mg/kg of body weight to mice, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 51.8 and 23 microg/ml, 79.5 and 46 microg. h/ml, 0.8 and 0.85 h, and 21 and 25 ml/h, respectively. Systemic candidiasis and aspergillosis were established in CD-1 male mice infected with Candida albicans or Aspergillus fumigatus. For systemic candidiasis, compounds were given three times per day for seven consecutive days at 15, 30, 60, or 120 mg/kg/day. GM193663 and GM237354 showed dose-related efficacy against C. albicans, with 50% effective doses, 1 month after infection, of 25.2 and 10.7 mg/kg/dose, respectively. In experimental infections with A. fumigatus, GM237354 was given three times per day at 30, 60, or 120 mg/kg/day for five consecutive days. Animals treated with GM237354 demonstrated irregular responses. The survival of animals treated with GM237354 was 0, 30, and 0% at 30, 60, and 120 mg/kg/day, respectively. The therapeutic efficacy of GM193663 and GM237354 against Pneumocystis carinii was studied in an experimental P. carinii pneumonia (PCP) rat model. After a subcutaneous dose of 10 mg/kg given to rats, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 6.6 and 7.2 microg/ml, 8.5 and 11.8 microg. h/ml, 0.7 and 0.8 h, and 230 and 133 ml/h, respectively. To induce spontaneous PCP, rats were chronically immunosuppressed with dexamethasone. Infected animals were treated twice daily for 10 days at 0.2, 2, or 10 mg/kg/day. The therapeutic effect was estimated by the reduction in the number of cysts in the lungs of treated versus untreated animals. GM193663 and GM237354 significantly reduced the mean (+/- standard deviation) log number of cysts from 7.6 +/- 0.2 in the untreated group to 4.7 +/- 0.2 and 4.6 +/- 0.1, respectively, when the drugs were administered at a dose of 2 mg/kg/day. The log number of cysts was also reduced in infected animals given lower doses of the compounds (0.2 mg/kg/day). In summary, GM193663 and GM237354 are new sordarin derivatives that may potentially play a major role in the treatment of candidiasis and PCP. Further testing with Aspergillus in other animal models is warranted.

Animals↗
PubMed2000

v-Src generates a p53-independent apoptotic signal.

Evasion of apoptosis appears to be a necessary event in tumor progression. Some oncogenes, such as c-myc and E1A, induce apoptosis in the absence of survival factors. However, others, such as bcl-2 and v-src, activate antiapoptotic pathways. For v-Src, these antiapoptotic pathways are dependent on the function of Ras, phosphatidylinositol (PI) 3-kinase, and Stat3. Here we asked whether v-Src can activate a proapoptotic signal when survival signaling is inhibited. We show that when the functions of Ras and PI 3-kinase are inhibited, v-src-transformed Rat-2 fibroblasts undergo apoptosis, evidenced by loss of adherence, nuclear fragmentation, and chromosomal DNA degradation. The apoptotic response is dependent on activation of caspase 3. Under similar conditions nontransformed Rat-2 cells undergo considerably lower levels of apoptosis. Apoptosis induced by v-Src is accompanied by a loss of mitochondrial membrane potential and release of cytochrome c and is blocked by overexpression of bcl-2, indicating that it is mediated by the mitochondrial pathway. However apoptosis induced by v-Src is not accompanied by an increase in the level of p53 and is not dependent on p53 function. Thus v-Src generates a p53-independent proapoptotic signal.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy.

OBJECTIVE: To determine the long-term effects of iron deficiency in infancy. DESIGN: Longitudinal follow-up study of children who had been tested and treated for iron deficiency as infants. SETTING: Periurban community near San Jose, Costa Rica. PARTICIPANTS: Of the original 191 participants, 87% were reevaluated at 11 to 14 years old (average age: 12.3 years). The children were free of iron deficiency and growing normally by US standards. Those who had chronic, severe iron deficiency in infancy (n = 48) were compared with those who had good iron status before and/or after iron therapy in infancy (n = 114). OUTCOME MEASURES: Comprehensive set of cognitive, socioemotional, and motor tests and measures of school functioning. RESULTS: Children who had severe, chronic iron deficiency in infancy scored lower on measures of mental and motor functioning. After control for background factors, differences remained statistically significant in arithmetic achievement and written expression, motor functioning, and some specific cognitive processes (spatial memory, selective recall, and tachistoscopic threshold). More of the formerly iron-deficient children had repeated a grade and/or been referred for special services or tutoring. Their parents and teachers rated their behavior as more problematic in several areas, agreeing in increased concerns about anxiety/depression, social problems, and attention problems. CONCLUSIONS: Severe, chronic iron deficiency in infancy identifies children who continue at developmental and behavioral risk >10 years after iron treatment.

Adolescent↗
PubMed1999

Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams.

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1999

Differential mechanisms of urethral smooth muscle relaxation by several NO donors and nitric oxide.

We have examined the mechanisms of action of a broad spectrum of nitric oxide (NO) donors, including several S-nitrosothiols, sodium nitroprusside (SNP) and nitroglycerine (GTN), in relation to their relaxant activity of urethral smooth muscle. For all the compounds examined, NO release (in solution and in the presence of urethral tissue), relaxation responses, elevations in cGMP levels and the effect of thiol modulators were evaluated and compared with the effect of NO itself. Whilst all NO donors, except GTN, released NO in solution due to photolysis or chemical catalysis, this release was not correlated with their relaxant activity in sheep urethral preparations, which were furthermore not affected by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (cPTIO; 0.3 mM). A substantial NO-generating activity was found for S-nitroso-L-cysteine (CysNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in the presence of urethral cytosolic fractions, suggesting metabolic activation to NO in the cytosol of the target tissue. In contrast, NO generation from S-nitroso-N-acetyl-L-cysteine (N-ac-CysNO), S-nitrosoglutathione (GSNO) and SNP were reduced by the presence of urethral homogenate and/or subcellular fractions, suggesting direct NO transfer to tissue constituents. NO donors and NO gas induced dissimilar degrees of cGMP accumulation in urethral tissue, while they were essentially equipotent as urethral relaxants. Furthermore, 1H-[1,2,4] -oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ; 10 microM) inhibited both relaxation and cGMP accumulations, but with different potency for the different compounds. Oxidation of sarcolemmal thiol groups with 5-5'-dithio-bis[2-nitrobenzoic acid] (DTNB; 0.5 mM) enhanced relaxations to GSNO, an effect that was reversed by dithiotreitol (DTT; 1 mM), suggesting a direct effect through nitrosylation/oxidation reactions at the cell membrane, while relaxations to NO and to all the other compounds were not affected by these treatments. Finally, photodegradation of SNP induced the formation of a stable intermediate that still evoked NO-cGMP-mediated relaxations. This indicates that the assumption that SNP is fully depleted of NO by exposure to light should be revised. It can be concluded that important differences exist in the mechanisms by which distinct NO donors relax urethral smooth muscle and they cannot be regarded simply as NO-releasing prodrugs.

Alkylation↗
PubMed1999

Angiotensin II stimulates the Na+/H+ exchanger in human umbilical vein endothelial cells via AT1 receptor.

Angiotensin II (Ang II) has an important role in cardiovascular regulation and in the control of electrolyte balance, and its role in the regulation of Na+ transcellular movements through its actions on the activity of Na+/K+ ATPase is well documented. We showed previously that human umbilical vein endothelial cells (HUVEC) express the Ang II type 1 (AT1) receptor, which mediates Ang II modulation of Na+/K+ ATPase activity (1). We here investigate the effects of Ang II on the activity of the Na+/H+ exchanger in HUVEC. When compared with controls, incubation of HUVEC for 20 min with different concentrations of Ang II provoked significant increases in Na+/H+ activity. The stimulation was dose dependent between 1 and 10 nM Ang II and varied with time of incubation up to 20 min. The maximal response, obtained with 10 nM Ang II after 20 min treatment, resulted in a 65% increment in Na+/H+ activity. Preincubation of HUVEC with 10 microM DuP753 blocked Na+/H+ activation by Ang II. These results suggest that the effects of Ang II on both the Na+/K+ ATPase and the Na+/H+ exchanger may increase the transendothelial flux of Na+ and are mediated by the AT1 receptor.

Angiotensin II↗
PubMed1999

Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.

Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts </=500/microL (22% had counts <200/microL) and required zidovudine for maternal health (24% received zidovudine before pregnancy). Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P=.005; 10.0% vs. 3.6% transmission for count <200 vs. >/=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

Adult↗
PubMed1999

Systemic pharmacokinetics and cellular pharmacology of zidovudine in human immunodeficiency virus type 1-infected women and newborn infants.

Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.

Adolescent↗
PubMed1999

Aneurysmal bone cyst of the temporal bone.

OBJECTIVE AND IMPORTANCE: Aneurysmal bone cysts (ABC) are benign bone neoplasms which typically involve the spine and long bones. We present a rare case of an ABC in the temporal bone with significant cerebellar compression. CLINICAL PRESENTATION: The patient was a young boy who presented with several weeks of left posterior auricular pain. Computed tomography, magnetic resonance imaging and angiogram showed an expansile bone neoplasm involving the left petrous temporal bone. INTERVENTION: A retrosigmoid-transmastoid craniectomy was performed, and total removal of the bone lesion was achieved. The pathological examination revealed the diagnosis of ABC. CONCLUSION: The postoperative course was uneventful, and the imaging studies demonstrated total removal of the neoplasm. This case represents the imaging and surgical management of a rare ABC in the temporal bone. This diagnosis should be considered in the differential of bone neoplasms in this region.

Bone Cysts, Aneurysmal↗
PubMed1999

Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1.

In vertebrates, the hedgehog family of cell signaling proteins and associated downstream network components play an essential role in mediating tissue interactions during development and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer and other tumors. The mammary gland is a specialized skin derivative requiring epithelial-epithelial and epithelial-stromal tissue interactions similar to those required for development of other organs, where these interactions are often controlled by hedgehog signaling. We have investigated the role of the Patched-1 (Ptc1) hedgehog receptor gene in mammary development and neoplasia. Haploinsufficiency at the Ptc1 locus results in severe histological defects in ductal structure, and minor morphological changes in terminal end buds in heterozygous postpubescent virgin animals. Defects are mainly ductal hyperplasias and dysplasias characterized by multilayered ductal walls and dissociated cells impacting ductal lumens. This phenotype is 100% penetrant. Remarkably, defects are reverted during late pregnancy and lactation but return upon involution and gland remodeling. Whole mammary gland transplants into athymic mice demonstrates that the observed dysplasias reflect an intrisic developmental defect within the gland. However, Ptc1-induced epithelial dysplasias are not stable upon transplantation into a wild-type epithelium-free fat pad, suggesting stromal (or epithelial and stromal) function of Ptc1. Mammary expression of Ptc1 mRNA is both epithelial and stromal and is developmentally regulated. Phenotypic reversion correlates with developmentally regulated and enhanced expression of Indian hedgehog (Ihh) during pregnancy and lactation. Data demonstrate a critical mammary role for at least one component of the hedgehog signaling network and suggest that Ihh is the primary hedgehog gene active in the gland.

Alagille Syndrome↗
PubMed1999

Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Adolescent↗
PubMed1998

Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study.

OBJECTIVE: To determine the safety of the zidovudine (ZDV) regimen utilized in the Pediatric AIDS Clinical Trial Group (ACTG) 076 study. DESIGN: ACTG 076 was a randomized, double-blind, placebo-controlled trial which demonstrated that a ZDV regimen could prevent mother-to-child HIV-1 transmission. Infants were followed through 18 months of age and women were followed through 6 months postpartum. METHODS: Maternal complications, pregnancy outcomes, growth and development of the uninfected infants, and HIV-1 disease progression in the women were monitored prospectively. RESULTS: Maternal therapy was well tolerated. There was no serious pattern of adverse pregnancy outcomes associated with ZDV use. Amongst the ZDV-exposed infants, the only recognized toxicity was anemia within the first 6 weeks of life; the risk for anemia was not associated with premature delivery, duration of maternal treatment, degree of maternal immunosuppression, or maternal anemia. ZDV treatment was not associated with an increased incidence of newborn structural abnormalities. At 18 months of age, uninfected infants did not differ in growth parameters or immune function. No childhood neoplasias were reported in either group. In the women, at 6 months postpartum, there were no differences in clinical, immunologic, or virologic disease progression. CONCLUSION: There were no identified problems that would alter current recommendations for the routine use of ZDV for the prevention of mother-child HIV-1 transmission.

Anti-HIV Agents↗
PubMed1998

Osteolysis associated with cemented total knee arthroplasty.

Osteolysis has not been mentioned as a complication or cause of failure of cemented total knee arthroplasties in long-term follow-up studies. We are aware of a single case report of osteolysis after cemented total knee arthroplasty. We report the case of an 87-year-old woman with massive osteolysis beneath a cemented tibial component.

Aged↗
PubMed1998

Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with colorectal cancer: inhibitory effect on cytotoxicity.

A positive correlation between the level of ICAM-1 in serum and the stage of neoplastic processes has been demonstrated. We studied ICAM-1 serum concentration in 27 colorectal cancer patients and investigated the effect of this molecule on cellular aggregation and toxicity. ICAM-1 serum concentration in the group of patients was significantly higher (P < 0.01) than in normal controls and was related to tumour stage. Patient sera inhibited both the formation of cellular aggregates and the percentage of specific lysis, the effect being lost when the serum was depleted of ICAM-1. These results suggest that the release of soluble ICAM-1 may represent a mechanism of tumour escape.

Aged↗