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Biomedical subjects

C Gonzalez

Publications and source records attributed to C Gonzalez.

At least 109 records · Page 6Linked to original sources
PubMed1998

Risk factors in necrotizing fasciitis: a case involving Cryptococcus neoformans.

Necrotizing fasciitis is a destructive soft tissue infection that is most typically caused by group A streptococci or a combination of facultative and anaerobic bacteria. Patients at risk for the development of necrotizing fasciitis often have compromised immune function or poor tissue perfusion. This report describes a case of necrotizing fasciitis caused by Cryptococcus neoformans, a pathogen not previously associated with this primary destructive soft tissue infection. The process occurred in a patient at risk for the development of opportunistic infection. We briefly review the risk factors for the development of necrotizing fasciitis and the typical bacteriologic findings. Cryptococcal infections and their treatment are described. Despite the uncommon pathogen, the treatment of this patient followed established principles-prompt surgical intervention and systemic antimicrobial therapy tailored to the offending organisms.

Adult↗
PubMed1998

Effects of almitrine bismesylate on the ionic currents of chemoreceptor cells from the carotid body.

Almitrine is a drug used in the treatment of hypoxemic chronic lung diseases such as bronchitis and emphysema because it is a potent stimulant of the carotid bodies in human and different animal species that produces a long-lasting enhancement of alveolar ventilation, ameliorating arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic currents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the patch-clamp technique. Almitrine at concentrations up to 10 microM did not affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of almitrine significantly inhibited the Ca2+-dependent component of K+ currents in rat chemoreceptor cells. This effect of almitrine on the Ca2+-dependent component of K+ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparation, almitrine inhibited the activity of a high-conductance (152 +/- 13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect was 0. 22 microM. The inhibitory effect of almitrine on Ca2+-dependent K+ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca2+-dependent K+ channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug.

Almitrine↗
PubMed1998

Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients.

The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.

Adult↗
PubMed1997

Stimulus-specific mobilization of dopamine and norepinephrine stores in cat carotid body.

The catecholamines (CAs), dopamine (DA) and norepinephrine (NE), are synthesized and stored in carotid body chemosensory type I cells. Previous studies in our laboratory demonstrated that low concentrations of nicotine preferentially evoke the release of NE from rabbit type I cells, whereas hypoxia mobilizes DA and NE in proportion to their stores in the tissue. The primary objective of the present study was to examine whether hypoxia, nicotine and elevated concentrations (30 mM) of K+ evoke the preferential release of DA vs. NE from cat carotid bodies superfused in vitro. In this species, where tissue stores of DA and NE are nearly equal, hypoxia evoked the preferential release of DA from normal carotid bodies. This pattern of release evoked by low O2 was also present following chronic removal of the superior cervical ganglion, which eliminated NE contained in the sympathetic innervation to the carotid body. In contrast, nicotine and high-K+ preferentially mobilized NE in these sympathectomized animals. Sympathectomy also reduced the percent of DA (but not NE) content released from type I cells in response to any of the three stimuli. Our findings suggest that chemosensory type I cells possess stimulus-specific mechanisms for CA mobilization and that the sympathetic innervation modulates the metabolism and release of CAs in the cat carotid body.

Animals↗
PubMed1997

Long-term extractable compounds screening in surface water to prevent accidental organic pollution.

The organic composition of surface water (a canal network fed by the Rhône river, France) was studied over a period of 3 years. The spatial and temporal evolution of extractable organic compounds was determined by monitoring the water of the principal canal (72 km long) over 3 years and 139 compounds were detected at the ng/l concentration level. Using these data the organic fingerprints were constructed for every sampling point. These fingerprints depend on sampling dates and climatic conditions. Analysed compounds were classified according to two criteria: appearance frequency and average concentrations. Three classes were defined, corresponding to: organic background, occasional component and chronic component. The preponderance of organic background, corresponding to the natural organic fingerprint, indicates the high quality of this surface water. The proportion of some chemical families were calculated in order to assess their anthropogenic impact on the water. This study produced a databank which was useful as a reference for the monitoring and checking of water quality. Any anomaly disturbing organic fingerprints can thus rapidly be detected and identified by comparison with the databank, making better crisis management possible.

Environmental Monitoring↗
PubMed1997

Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.

BACKGROUND: The new protease inhibitors are potent inhibitors of the human immunodeficiency virus (HIV), and in combination with other antiretroviral drugs they may be able to cause profound and sustained suppression of HIV replication. METHODS: In this double-blind study, 97 HIV-infected patients who had received zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of lamivudine twice daily; or all three drugs. The patients were followed to monitor the occurrence of adverse events and changes in viral load and CD4 cell counts. RESULTS: The decrease in HIV RNA over the first 24 weeks was greater in the three-drug group than in the other groups (P<0.001 for each comparison). RNA levels decreased to less than 500 copies per milliliter at week 24 in 28 of 31 patients in the three-drug group (90 percent), 12 of 28 patients in the indinavir group (43 percent), and none of 30 patients in the zidovudine-lamivudine group. The increase in CD4 cell counts over the first 24 weeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each comparison). The changes in the viral load and the CD4 cell count persisted for up to 52 weeks. All the regimens were generally well tolerated. CONCLUSIONS: In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.

Adult↗
PubMed1997

Three-dimensional solution structure and stability of phage 434 Cro protein.

1H NMR resonances of the phage 434 Cro protein were assigned using standard 2D NMR methods, and its solution structure determined using 867 distance constraints in distance geometry (DIANA) calculations ultimately refined by restrained molecular dynamics (GROMOS). In the 20 best NMR structures, the average pairwise backbone and heavy atom RMSDs are 0.63 +/- 0.14 and 1.53 +/- 0.15 A, respectively, for the structurally well-defined residues 4-65. Residues 1-3 and 66-71 at the N- and C-termini are structurally disordered. The region 4-65 includes five alpha-helices and tight turns which define the hydrophobic core of the protein. The backbone and heavy atom RMSDs for residues 4-65 are 0.92 +/- 0.12 and 1.99 +/- 0.12 A, respectively, for the NMR versus the crystal structures, but there are significant differences in the side-chain conformations and solvent accessibilities for some core residues. Analytical ultracentrifugation experiments confirm that 434 Cro is monomeric even at the high NMR concentrations. 434 Cro folding under NMR solution conditions is two-state as indicated by coincident urea denaturation curves from circular dichroism and intrinsic fluorescence measurements. They yield values for 434 Cro stability which show good correspondence to the free energy for global unfolding determined by NMR hydrogen exchange measurements for the slowest exchanging amide protons.

Amino Acid Sequence↗
PubMed1997

The Drosophila gene abnormal spindle encodes a novel microtubule-associated protein that associates with the polar regions of the mitotic spindle.

abnormal spindle, a gene required for normal spindle structure and function in Drosophila melanogaster, lies immediately adjacent the gene tolloid at 96A/B. It encodes a 220-kD polypeptide with a predicted pI of 10.8. The recessive mutant allele asp1 directs the synthesis of a COOH terminally truncated or internally deleted peptide of approximately 124 kD. Wild-type Asp protein copurifies with microtubules and is not released by salt concentrations known to dissociate most other microtubule-associated proteins. The bacterially expressed NH2-terminal 512-amino acid peptide, which has a number of potential phosphorylation sites for p34(cdc2) and MAP kinases, strongly binds to microtubules. The central 579-amino acid segment of the molecule contains one short motif homologous to sequences in a number of actin bundling proteins and a second motif present at the calmodulin binding sites of several proteins. Immunofluorescence studies show that the wild-type Asp protein is localized to the polar regions of the spindle immediately surrounding the centrosome. These findings are discussed in relation to the known spindle abnormalities in asp mutants.

Amino Acid Sequence↗
PubMed1997

Essential role for gamma-tubulin in the acentriolar female meiotic spindle of Drosophila.

Microtubule nucleation in vivo requires gamma-tubulin, a highly conserved component of microtubule-organizing centers. In Drosophila melanogaster there are two gamma-tubulin genes, gammaTUB23C and gammaTUB37C. Here we report the cytological and molecular characterization of the 37C isoform. By Western blotting, this protein can only be detected in ovaries and embryos. Antibodies against this isoform predominantly label the centrosomes in embryos from early cleavage divisions until cycle 15, but fail to reveal any particular localization of gamma-tubulin in the developing egg chambers. The loss of function of this gene results in female sterility and has no effect on viability or male fertility. Early stages of oogenesis are unaffected by mutations in this gene, as judged both by morphological criteria and by localization of reporter genes, but the female meiotic spindle is extremely disrupted. Nuclear proliferation within the eggs laid by mutant females is also impaired. We conclude that the expression of the 37C gamma-tubulin isoform of D. melanogaster is under strict developmental regulation and that the organization of the female meiotic spindle requires gamma-tubulin.

Animals↗
PubMed1997

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map.

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T2-weighted fast spin-echo (FSE), and T1-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T1 based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.

Animals↗
PubMed1997

Osteoarticular and muscle infectious lesions in patients with the human immunodeficiency virus.

Between 1988 and 1995, 1832 HIV positive patients were evaluated in our institution. We studied the epidemiologic, immunologic and bacteriologic data, laboratory tests, and X-Ray films in those with musculoskeletal infection. We reviewed twenty-one cases of musculoskeletal infection in twenty patients aged 23-35 years (mean 28,6 years, M:F= 15:5). In all of them risk factor for HIV was intravenous drug abuse. The number of CD4 positive lymphocytes ranged from 0,003 to 0,5 10(9)/l. Staphylococcus aureus was the organism responsible of the infection in twelve cases, all active intravenous drug abusers at the time the diagnosis was done. The remaining causative agents were: Mycobacterium tuberculosis (3 cases), Candida albicans (2 cases), Salmonella subgroup 1 (1 case), Neisseria gonorrhoeae (1 case), Pseudomona aeruginosa (1 case) and Streptococcus agalactiae (1 case). Fifteen infections were diagnosed between 1988 and 1991 and 6 between 1992 and 1995. Musculoskeletal infectious lesions in HIV positive patients in our country are related in the majority of cases to intravenous drug abuse. In the last four years due to a National medical health care plan conducted to educate this group of people the number of musculoskeletal infections is decreasing.

AIDS-Related Opportunistic Infections↗
PubMed1997

Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study.

Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate increase in the proinsulin to insulin ratio has been proposed as a marker of compromised insulin secretion. We examined the association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin, a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years) to NIDDM even in obese populations.

Adult↗
PubMed1997

Oil enriched diets and behavioral parameters in rats' recovery from early undernutrition.

The effect of oil enriched diets on sexual and exploratory behavior has been studied in male rats undernourished in utero and during lactation. At 20 days of age, for a period of 4 months, these animals were fed with 3 different diets: standard diet, standard diet enriched with 7% soybean oil, and standard diet enriched with 7% olive oil. A control group eating standard diet was also studied. Sexual behavior, open-field and nocturnal spontaneous locomotor activity were studied at 16-20 weeks of age. Undernutrition produced decreased body weight, and the experimental diets were not effective in growth recovery. Undernourished animals eating oil-enriched diets displayed lower nocturnal spontaneous locomotor activity, less time spent in central squares, and a lower number of rearing episodes than undernourished animals eating the standard diet; the number of peripheral squares entered was, however, significantly increased. Experimental groups eating oil diets showed a statistically significant increase in the number of ejaculating males and in the total number of ejaculations compared with experimental rats eating standard diet. These findings suggest that early undernutrition produces permanent behavioral alterations in male rats, but that the sexual behavior deficit could be reversed by feeding our oil-enriched diets from weaning. The diet enriched with soybean oil seems more effective in the rehabilitation of sexual behavior.

Animals↗
PubMed1997

Prenatal stress alters the size of the rostral anterior commissure in rats.

In rodents and other mammals, prenatal stress disrupts both sexual differentiation and sexual behavior. The present study examined the area of the anterior division of the anterior commissure (the Aca) in coronal, thionin-stained sections of prenatally stressed (P-S), and control male and female rats. Pregnant rats were exposed to thrice-daily heat, light, and restraint stress or left undisturbed during days 15-22 of pregnancy. Adult P-S and control males and females were killed, perfused, and their brains removed. Serial coronal sections (total of approximately 200 microm) through the rostral portion of the Aca (the rAca) were taken and stained with thionin. The sections were examined and traced under x25 using computerized microscopy to obtain the area in mm2. The data revealed that control females had a larger rAca compared to control males, and that P-S males had a larger rAca compared to control males; further, control males and P-S females were not significantly different, nor were control females and P-S males. These results suggest that, in rats, the Ac may be sexually dimorphic (in a direction similar to that described in humans) and that prenatal stress an event that modifies sex-typical behavior, physiology, and neuroanatomy reverses that sex difference.

Aging↗