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Biomedical subjects

C Cuello

Publications and source records attributed to C Cuello.

At least 37 records · Page 2Linked to original sources
PubMed1994

Encapsulated genetically engineered fibroblasts: release of nerve growth factor and effects in vivo on recovery of cholinergic markers after devascularizing cortical lesions.

Genetically engineered rat fibroblasts producing nerve growth factor (NGF) were encapsulated in alginate-polylysine-alginate gels with the objective to produce viable "minifactories" continuously producing and secreting NGF into the rat brain. Microencapsulated fibroblasts (NGF secretors and NGF non-secretors) were placed onto the surface of the lesioned rat cortex (unilateral devascularizing lesion) and animals were sacrificed 30 days after surgery. Fibroblasts NGF-non secreters normally produce tumors after implantation, therefore, they were irradiated prior to encapsulation. Three other experimental groups were studied in parallel: non-lesioned (controls), lesioned rats receiving "empty" alginate spheres and lesioned animals without treatment and microspheres. Biochemical analysis of microdissected brain tissues of lesioned animals treated with encapsulated NGF-secretor fibroblasts showed a significant increase in choline acetyltransferase (ChAT) activity in cortices adjacent to the lesion but not far from it (entorhinal cortex). This may indicate a gradient of concentration of the released NGF and/or differential responsivity of lesioned vs non-lesioned target tissue. ChAT enzymatic activity in the microdissected nucleus basalis magnocellularis (NBM) was significantly decreased (P < 0.05) in all lesioned animals treated with spheres without fibroblasts and those with fibroblasts not secreting NGF. Morphometric analysis of ChAT-IR and low affinity NGF-receptor IR cholinergic neurons in the middle portion of the NBM shows a prevention of neuronal shrinkage and extensive neuropil in animals treated with microencapsulated NGF-secretor fibroblasts. The results of this study demonstrate that NGF from encapsulated genetically engineered fibroblasts can be secreted for at least long enough to prevent degenerative changes of cholinergic neurons in the NBM.

Alginates↗
PubMed1994

Radiofrequency catheter ablation of the atrioventricular junction by a supravalvular noncoronary aortic cusp approach.

Radiofrequency catheter ablation of the atrioventricular junction is usually achieved from either the right or left atrioventricular junction. We describe a new approach in which the atrioventricular junction was successfully ablated from the supravalvular region of the noncoronary cusp of the aortic valve in an unusual patient in whom conventional approaches were unsuccessful.

Atrial Fibrillation↗
PubMed1994

Usefulness of oral quinidine-mexiletine combination therapy for sustained ventricular tachyarrhythmias as assessed by programmed electrical stimulation when quinidine monotherapy has failed.

In patients presenting with sustained ventricular tachyarrhythmias, when oral quinidine monotherapy fails as determined by programmed electrical stimulation, the degree of benefit observed with combination therapy with mexiletine is debated. We prospectively studied 20 consecutive patients (16 men and 4 women) aged 33 to 77 years (mean age, 62 +/- 11 years) who were treated with maximally tolerated quinidine and mexiletine combination therapy and who had ventricular tachyarrhythmias induced at baseline and during oral quinidine monotherapy. Coronary artery disease was present in 19 patients (95%). Programmed electrical stimulation was performed at 2 drive train cycle lengths with up to 3 extrastimuli at two ventricular sites. During follow-up study with combination quinidine-mexiletine therapy ventricular tachyarrhythmias were rendered noninducible in four patients (20%). The remaining 16 patients showed a significant slowing of their tachycardia cycle length (267 +/- 56 msec baseline vs 320 +/- 75 msec with quinidine vs 345 +/- 53 msec with combination therapy, p < 0.05). There was also an increase in the mean QTc interval (452 +/- 50 msec baseline vs 477 +/- 79 msec after quinidine vs 486 +/- 65 msec with combination quinidine-mexiletine therapy, p = not significant) and in the mean ventricular effective refractory period (246 +/- 25 msec baseline vs 281 +/- 37 msec after quinidine vs 290 +/- 25 msec with combination quinidine-mexiletine therapy, p < 0.05). We conclude that sustained ventricular tachyarrhythmias induced during quinidine monotherapy were rendered noninducible by oral combination therapy with quinidine-mexiletine in 20% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A unique pulse generator safety feature for bipolar lead fracture.

In this report, we describe two pacemaker dependent patients with outer-coil fractures in their bipolar ventricular leads who averted potentially catastrophic consequences because of a new safety feature incorporated into their pulse generators (Intermedics Cosmos II, model 284-05). Both patients were asymptomatic; the malfunctions were discovered at routine pacemaker evaluation. Magnet application resulted in symptomatic loss of ventricular capture. In each instance, the pulse generator detected an outer-coil fracture and reprogrammed itself from bipolar DDD to unipolar DOO pacing to prevent loss of capture. Subsequent lead replacement resulted in resumption of normal function. We suggest that this feature be incorporated into all devices with programmable polarity.

Aged↗
PubMed1992

A tutorial/essay project to expand the learning experience in undergraduate medical pharmacology.

To lessen fact overload and to enhance the teaching of pharmacologic principles in an undergraduate course we introduced a tutorial/essay project into our traditional lecture-based course. Under the guidance of a faculty tutor, each student researched an assigned topic, developed a paper incorporating the results of the literature review and his or her own attitudes and formally discussed and answered questions on the topic with the tutor. Students and tutors were enthusiastic about this learning experience especially in that it required independent student-centred activity, provided opportunity for useful student/tutor interaction and helped students to learn to integrate scientific information with their own thoughts and ideas.

Curriculum↗
PubMed1990

Gastric precancerous process in a high risk population: cross-sectional studies.

The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Atrophy↗
PubMed1990

Gastric precancerous process in a high risk population: cohort follow-up.

In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.

Atrophy↗
PubMed1990

Risk factors of gastric precancerous lesions in a high-risk Colombian population. I. Salt.

A case-control study for stomach cancer was conducted in a high-risk population in Nariño, Colombia to determine the risk of gastric precancerous lesions associated with salt intake measured by sodium-to-creatinine ratio of a single urine sample. Gastric biopsies and urine samples were collected from 263 individuals. Urinary sodium-to-creatinine ratios were studied in relation to histological data from the biopsies. Significantly high odds ratios for precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) were associated with higher sodium-to-creatinine ratios. Adjusted odds ratios (OR) of 2.50 for chronic atrophic gastritis and 7.24 for dysplasia were found. The association with intestinal metaplasia was weaker and not significant (OR = 1.57). Furthermore, an excess risk associated with adding salt to food at the table was found among patients with precancerous lesions (OR = 1.80). These findings support the two-step involvement of salt in the process of gastric precancerous lesions.

Adult↗
PubMed1990

Risk factors of gastric precancerous lesions in a high-risk Colombian population. II. Nitrate and nitrite.

Gastric nitrite content was studied in relation to precancerous lesions of the stomach in a case-control study conducted in a high-risk Colombian population. The proportion of detectable nitrite in gastric juice and the mean pH were significantly higher among those with precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) than among the controls (normal and superficial gastritis); the proportion and mean pH increased with the progression of histological changes from normal to dysplasia. Nitrite was not detectable in gastric juice with a pH less than 5.0. A positive association was found between the proportion of detectable nitrite and the risk of gastric precancerous lesions. Odds ratios of 4.39 for intestinal metaplasia and 24.72 for dysplasia remained significant after controlling for confounders. This finding suggests that nitrite may be a precursor of a mutagen that targets gastric epithelial cells.

Case-Control Studies↗
PubMed1987

Genetic etiology of gastric carcinoma: II. Segregation analysis of gastric pH, nitrate, and nitrite.

A study of gastric pH, nitrate, and nitrite in 110 families collected as part of a cohort from the Narino region of Colombia is presented. All three traits are familial and have a significant linearly increasing age trend. Gastric pH has a clear bimodal distribution but does not show Mendelian segregation. The nitrate distribution is slightly skewed, but generational heterogeneity explains the data best. Gastric nitrite is also biomodal with a clear break at concentration 1.08 micrograms/ml, and 74% of the observations at zero concentration; it shows a recessive Mendelian segregation with significant residual spouse correlation. This model also fits the data best when nitrite is dichotomized into detected (measurable) and undetected values. The estimated frequency of the recessive allele is .57, so that an estimated 32% of the population sampled are recessives. Recessives whose spouses have measurable nitrite have an estimated penetrance of 99.3% at age 30 years, whereas those whose spouses have zero or undetected nitrite have a penetrance of only 8.8% at age 30 years. It appears that gastric nitrite, and, from our previous study of these families, chronic atrophic gastritis are important biologic markers for the early identification of persons predisposed to gastric cancer.

Adult↗
PubMed1986

Cholinergic and GABAergic neurotoxicity of some alkylating agents.

A series of nitrogen mustard derivatives was tested for neurotoxic effects on cholinergic and GABAergic markers at three rat brain regions: hippocampus, striatum and cortex. All compounds were administered intracerebroventricularly, and the enzymatic activities were measured 7 days after treatment. The effects of synthesised nitrogen mustard derivatives with indole, quinoline and hemicholinium backbone structures were compared. Of these compounds, only the hemicholinium analogue showed some preferential neurotoxicity to cholinergic neurones, thus offering a basis for designing novel, more specific cholinergic neurotoxins.

Alkylating Agents↗
PubMed1986

Genetic etiology of gastric carcinoma: I. Chronic atrophic gastritis.

Scientific evidence has accumulated to show that chronic atrophic gastritis (CAG) is a precursor of gastric carcinoma, especially its intestinal histologic type; thus the etiology of CAG is of interest. Data on 110 families (557 individuals) collected as part of a large cohort from the Narino region of Colombia, South America, are analyzed to determine the familiality of CAG as a risk factor, and the possible involvement of a major gene in its etiology. We found that age and having an affected mother are important risk factors. In the sample, 45% are affected; 56% of individuals above 30 are affected, whereas only 28% of those 30 and under are affected; 48% of those with affected mothers are affected, but only 7% of those with unaffected mothers are affected. A positive spouse association was confounded with age. Sex and an affected father are not significant risk factors. The genetic (segregation) analysis showed Mendelian transmission of a recessive autosomal gene with penetrance dependent on age and mother's CAG status. Homozygous recessives account for an estimated 61% of the sampled population and have penetrance reaching 72% at age 30 if the mother is affected, and 41% if the mother is not affected. Carriers and non-carriers, who make up an estimated 39% of the sampled population, have an appreciable estimated risk after age 50. The environment, particularly diet, as the sole determinant of CAG needs reevaluation; some combined action of genes and environment seems more plausible.

Age Factors↗
PubMed1986

Striato-nigral dynorphin and substance P pathways in the rat. I. Biochemical and immunohistochemical studies.

The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The hypothalamic arcuate nucleus-median eminence complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons.

In this paper, we describe the results of a series of experiments which have examined the distribution within the arcuate nucleus of the hypothalamus of neurons containing the following immunoreactivities: TH-LI, GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-LI, Leu-ENK-LI, Met-ENK-7-LI, Met-ENK-8-LI, metorphamide-LI, DYN-LI, NPY-LI, SOM-LI, FMRFamide-LI, and CLIP-LI and ependymal tanycytes containing DARPP-32-LI. Using elution-restaining and double antibody staining techniques we have established numerous patterns of coexistence of these various neurotransmitters and neuropeptides. Thus, neurons containing TH-LI were, in some instances, also found to contain GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-8-LI, Leu-ENK-LI, or DYN-LI or combinations of these compounds. For example, some TH-IR neurons also contained GAL-LI and GRF-LI, while other TH-IR. neurons were also seen to contain GRF- and NT-LI. These neurons may, in fact, contain even more compounds. NPY-IR neurons and those containing SOM-LI and CLIP-LI were distinct and separate from those containing TH-LI. The distribution of these different neurochemical types of neurons and their patterns of coexistence are summarized in Fig. 34, while the relative distribution patterns of immunoreactive fibres in the median eminence are summarized in Fig. 35.

Animals↗
PubMed1985

Serum micronutrient levels in relation to gastric pathology.

As part of an ongoing cohort study of gastric cancer precursors in Nariño, Colombia, blood levels of ascorbic acid, vitamin E, retinol, pre-albumin, retinol binding protein and carotenoids were measured and correlated with histopathologic findings of gastric biopsies. Carotene levels in both sexes and vitamin E levels in males were significantly lower in subjects with gastric dysplasia than in subjects with normal mucosa and subjects with less advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia). No other significant correlations were found.

Adolescent↗
PubMed1985

Sodium intake and gastric cancer.

To test the hypothesis that excessive intake of sodium chloride is a factor in gastric carcinogenesis, urinary excretion of sodium and creatinine was measured in Colombian subjects. Age, sex, weight, and height regression slopes for creatinine excretion were more similar in Colombia than in other countries. Sodium/creatinine (S/C) ratios correlated with 24-h urinary excretion of sodium revealed higher sodium excretion in populations with higher gastric cancer rates. The S/C ratios were not affected by circadial rhythms, making it possible to use single urine samples to investigate interpopulation differences in sodium excretion.

Age Factors↗