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Biomedical subjects

J A Gomez

Publications and source records attributed to J A Gomez.

At least 19 recordsLinked to original sources

Conformational free energies of 1,2-dichloroethane in nanoconfined methanol.

Monte Carlo simulations have been used to construct free energy surfaces of 1,2-dichloroethane dissolved in methanol confined in hydrophobic spherical cavities of varying size (10-15 A) and solution density (0.6-0.79 g/cm3). The free energy surfaces are functions of two variables: the (center-of-mass) distance from the cavity wall of 1,2-dichloroethane and the Cl-C-C-Cl dihedral angle. Umbrella sampling and the weighted histogram analysis method were used to obtain accurate results for the free energy in these two degrees of freedom. Our results indicate that the conformational equilibrium and the barrier to internal rotation of the 1,2-dichloroethane depend on the position in the cavity. The results are discussed in the context of the solvent density, orientational distributions, and packing effects.

Journal Article↗

Characterization of a vaccinia virus strain used to produce smallpox vaccine in Argentina between 1937 and 1970.

Due to recent political developments, smallpox has re-emerged as a serious threat. We recovered and characterized an old batch of smallpox vaccine, Malbrán strain, produced between 1945 and 1949. The virus was re-isolated and characterized by sequence analysis and biological activity in animals. Phylogenetic analysis using the hemagglutinin and A45R genes showed that the Malbrán strain was closely related to the Lister strain of vaccinia virus. In animals, the Malbrán strain exhibited low pathogenicity, confirming historical records. Mice immunized with the Malbrán strain survived a lethal challenge with cowpox virus. Thus, this strain of vaccinia virus remains a viable candidate as a smallpox vaccine.

Argentina↗

Effects of birth date and order in lactation performance of Iberian red deer (Cervus elaphus hispanicus).

This study discriminated between 2 effects (birth date and presence of older calves) assessed jointly in previous studies. Birth date delay produced similar effects to those reported previously: reduced milk and milk nutrient production in late-calving hinds, concentration of milk, substitution of protein by fat, greater body weight losses of dams (hinds), and reduced calf growth. Hinds in a group consisting of early- and late-born calves produced more milk, and calves grew more than their isolated counterparts. Evidence exists for consequences of foster suckling by early-born calves in mixed groups of early- and late-born calves at the end of the standard birth period, because these calves grew more than predicted by the milk production of their dams. In contrast, no detrimental effect was found in late-born calves of this group. Lack of differences might be due to the excess of hind milk production during the first 5 wk of lactation previously recorded in other experiments.

Animals↗

Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion.

The recently proposed World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of flat urothelial lesions expands the definition traditionally used for urothelial (transitional cell) carcinoma in situ (CIS), basing its diagnosis predominantly on the severity of cytologic changes. Lesions now encompassed within the diagnosis of CIS exhibit an array of cytologic and architectural features, which have not been documented in detail. In this study, cases were examined with respect to histologic patterns and microinvasion (invasion into the lamina propria to a depth of less than 2 mm). Five major patterns of CIS, often occurring in the same specimen (160 patterns in 77 cases), were noted. Common to each pattern was the presence of high-grade cytologic atypia, the definitional feature. The patterns found include 1) large cell CIS with pleomorphism (57%), in which the cells had abundant cytoplasm and nuclear pleomorphism; 2) large cell CIS without nuclear pleomorphism (48%); 3) small cell CIS (14%), in which the cytoplasm was relatively scant and pleomorphism was usually minimal; 4) clinging CIS (40%), in which the urothelium was denuded with a patchy, usually single layer of atypical cells; and 5) cancerization of urothelium (16%) with either pagetoid spread (clusters or isolated single cells) or undermining or overriding of the normal urothelium. Carcinoma in situ with microinvasion into the lamina propria (13 cases: 3 of 77 CIS cases studied above and 10 additional cases) was evident as invasive cells with retraction artifact mimicking vascular invasion (77%, 10 cases); nests, irregular cords, and strands, or isolated single cells with desmoplasia (8%, 1 case); or absent stromal response (15%, 2 cases). Although the diagnostic terminology for all of these patterns, for the purposes of the surgical pathology report, should be simply urothelial CIS with no specific mention of the morphologic pattern, awareness of the histologic diversity of CIS will facilitate the diagnosis of this therapeutically and biologically critical flat lesion of the urothelium. These lesions may be associated with microinvasion, which may be clinically unsuspected and histologically subtle.

Carcinoma in Situ↗

Olive oil supplemented with vitamin E affects mitochondrial coenzyme Q levels in liver of rats after an oxidative stress induced by adriamycin.

In this study we have evaluated the supplementation of olive oil with vitamin E on coenzyme Q concentration and lipid peroxidation in rat liver mitochondrial membranes. Four groups of rats were fed on virgin olive, olive plus 200 mg/kg of vitamin E or sunflower oils as lipid dietary source. To provoke an oxidative stress rats were administered intraperitoneally 10 mg/kg/day of adriamycin the last two days of the experiment. Animals fed on olive oil plus vitamin E had significantly higher coenzyme Q and vitamin E levels but a lower mitochondrial hydroperoxide concentration than rats fed on olive oil. Retinol levels were not affected, by either different diets or adriamycin treatment. In conclusion, an increase in coenzyme Q and alpha-tocopherol in these membranes can be a basis for protection against oxidation and improvement in antioxidant capacity.

Animals↗

Evaluation of the vertical forces generated by the cervical biteplate facebow.

The biteplate facebow has been recommended for use in the correction of Class II malocclusions with deep overbites. This facebow is similar in design to the conventional cervical facebow with the addition of an inner bow metal plate. The plate presses against the maxillary incisors and prevents the patient from fully closing, thus acting as a biteplate. A test apparatus was constructed to simulate the force system present during application of the facebow. In this study, high resolution force transducers were used to measure the intrusive forces on the maxillary and mandibular incisors. Static force analysis techniques were then used to calculate the vertical force component of the first molars. Analyses were performed using a wide range of relative bow angles, neck strap tensions of 200 grams and 400 grams, and various mandibular incisor occluding forces. The molar eruptive forces of the biteplate facebow are found to exceed those of the standard cervical facebow by a low of 158% to a high of 537%, depending on the neck strap tension and the inner bow/outer bow angle. While the intrusive forces on the maxillary incisors were excessive, no intrusion is anticipated because the biteplate disarticulates the posterior teeth and the eruption of the unopposed maxillary molars would likely cause the occlusal plane to tip in a counter-clockwise direction. Consequently, the overbite correction would be obtained through maxillary molar eruption accompanied by occlusal plane tipping. Before considering use of the biteplate facebow, a patient's anticipated growth pattern, the magnitude of the intrusive forces and the treatment objectives should be evaluated.

Activator Appliances↗

Admission stool guaiac test: use and impact on patient management.

PURPOSE: A stool guaiac test is often performed on newly hospitalized patients as part of the admission evaluation. However, little is known regarding the value of testing stool obtained by digital rectal examination. We sought to document the use of the admission stool guaiac test in a teaching hospital, to determine its diagnostic yield, and to assess its potential benefit to patients. MATERIALS AND METHODS: We performed a retrospective review of the medical records for 264 consecutive patients admitted to internal medicine services during a single month, of whom 202 received a stool guaiac test on admission. Information was collected on the frequency of guaiac testing, indications for testing, test results, and diagnoses established. RESULTS: Criteria were established to distinguish "clinically indicated" from "routine" use of the admission stool guaiac test. Indicated tests were positive more often than routinely performed tests (35% versus 11%, p less than 0.001). Most patients with positive tests received further testing for gastrointestinal disease, whether or not the test was indicated. Of 104 patients with indications, 25 were ultimately found to have gastrointestinal lesions, most of which were clinically important. Of 98 patients tested routinely, only four had diagnoses established, of whom three had benign conditions. Four of five patients with cancer had clinical indications for testing. The fifth was diagnosed only after he experienced gross rectal bleeding several days after admission. CONCLUSIONS: Like other commonly applied diagnostic tests, the stool guaiac test obtained during the admission physical examination is best reserved for patients whose clinical presentation provides a reason for testing. In patients without clinical indications, the test is of uncertain value and only infrequently leads to important diagnoses.

Academic Medical Centers↗

Epidemiology of enteric adenovirus infection in prospectively monitored Argentine families.

To examine the role of enteric adenoviruses (EAV) in an urban area of Buenos Aires (Argentina), we prospectively studied faecal samples from 49 families of newborns. These were monitored weekly for diarrhoea for 2 years. A total of 180 samples from cases of diarrhoea and 766 samples obtained during diarrhoea-free periods were studied by dot-blot hybridization with an EAV-specific DNA probe. EAV were found in 6/180 (3.3%) cases of diarrhoea and 6/766 (0.8%) asymptomatic samples (P < 0.015). Incidence of EAV was 3.9 cases per 100 person-years in children < 60 months old. EAV-related diarrhoeas were slight and of short duration. In addition, 129 faeces from hospital out-patients, 1-30 months old, were also studied. EAV was identified in 7/129 cases (5.4%). These cases were 9.5 +/- 3.5 months old and the diarrhoea was mild or severe, of 3 +/- 1.5 days of duration. We suggest that EAV are low-risk causes of diarrhoea under natural conditions, although a few children may develop more severe diarrhoea. The diagnosis of EAV needs to be considered in these patients.

Adenovirus Infections, Human↗

Differential dose-related haematological effects of GM-CSF in pancytopenia: evidence supporting the advantage of low- over high-dose administration in selected patients.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional haematopoietin which can promote production of several blood cell lineages, though the predominant target cells are neutrophils, monocytes, and their precursors. Occasional undesirable clinical effects include eosinophilia, an increase in blasts, or thrombocytopenia. Here, we describe four patients who were treated with GM-CSF, at subcutaneous doses significantly lower than are conventional, and experienced an unusual response pattern. Three patients had severe pancytopenia associated with chronic lymphocytic leukaemia (CLL) or myelodysplastic syndrome (MDS) and exhibited an unexpected switch in the responsive lineage on high- versus very low-dose therapy. The two CLL patients developed marked eosinophilia (up to 10.0 x 10(9) cells/l) without an increase in neutrophils on 125-300 micrograms/m2/d of GM-CSF. In contrast, when the dose was lowered to 10 micrograms/m2/d, the neutrophils rose to physiological levels, without significant eosinophilia. The MDS patient showed a rapid rise in peripheral blasts (baseline level = 0; post-therapy level = 5.0 x 10(9)/l), without a change in other cell types, when receiving 60 micrograms/m2/d of GM-CSF. After GM-CSF was held, blasts returned to baseline levels; reinstituting therapy at the very low dose of 6 micrograms/m2/d was followed by an increase in platelet counts from 50 to 185 x 10(9)/l with only a minor increase in blasts. The fourth patient, who suffered from severe aplastic anaemia complicated by recurrent gastrointestinal haemorrhage, was only treated with the low-dose regimen. He showed a predominant platelet effect with counts rising from 9 to 169 x 10(9)/l. Very low-dose GM-CSF therapy was devoid of constitutional side effects. The biological implications of these GM-CSF responses are discussed. Our results indicate that, in some patients, GM-CSF may stimulate different target cells depending on the dose. Therefore, in contrast to the results of administration of many classical drugs, there may not always be a direct relationship between the amount of GM-CSF given and the optimal effect.

Adult↗

Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins.

In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure. Blood pressure was effectively reduced in all groups. Patients on hydrochlorothiazide showed a significant increase (P less than 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment. A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P less than 0.05) of treatment in patients on metoprolol. In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P less than 0.001) and 6 months (P less than 0.05), triglycerides increased after 6 (P less than 0.01) and 12 months (P less than 0.01), and LDL-C increased after 3 (P less than 0.05), 6 (P less than 0.001) and 12 months (P less than 0.01) of treatment, respectively. In 61% of the patients, three or more lipid parameters were affected during the study period. We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease.

Cholesterol↗

Apolipoprotein C subtype distribution in type 2 diabetes mellitus.

Plasma lipid levels and apolipoprotein C (apo C) composition of VLDL were investigated in a group of Type 2 diabetic patients at first attendance at the outpatient clinic and before any therapeutic intervention. Patients were distributed into two groups of 26 individuals, normo- and hyperlipidaemic, respectively, and compared with two matched control groups. Normolipidaemic diabetic patients had higher serum triglycerides, VLDL cholesterol, and lower HDL cholesterol than matched normolipidaemic control subjects. While hyperlipidaemic non-diabetic individuals showed increased apo C II and decreased apo C III-1 percentages when compared with normolipidaemic non-diabetic individuals (12.1 +/- 4.9 vs 8.5 +/- 3.2% and 44.0 +/- 6.7 vs 48.1 +/- 7.0%, respectively, mean +/- SD, both with p less than 0.05), the relative distribution of apo C III isoforms and apo C II was similar in both normo- and hyperlipidaemic diabetic patients.

Apolipoproteins C↗

Insulin action in early embryonic life: anti-insulin receptor antibodies retard chicken embryo growth but not muscle differentiation in vivo.

Insulin receptors are present in chicken embryos at day 2 of development and insulin stimulates embryonic growth and differentiation. Most important, anti-insulin antibodies cause either death or developmental retardation in chicken embryos of that age. To determine if the embryo's endogenous insulin acts through its own receptor, we compared the effects of anti-insulin antibodies to the effects of anti-insulin receptor antibodies on growth and differentiation indexes in the chicken embryo. While the anti-insulin antibody caused a dose-dependent decrease in growth parameters like weight, total protein, DNA, RNA, total creatine kinase activity and a marker of differentiation, the creatine kinase-MB, the anti-insulin receptor antibody decreased all parameters except the creatine kinase-MB. Many, but not all, of the effects of insulin in early embryos, thus, are mediated through the insulin receptor.

Animals↗

Insulin and insulin-like growth factor I both stimulate metabolism, growth, and differentiation in the postneurula chick embryo.

Chick embryos after 48 h of development (day 2) maintained in ovo provide an adequate model to study hormonal influences in early organogenesis in vertebrates. In previous studies at this (prepancreatic) stage of chick embryogenesis we demonstrated not only the presence of an insulin-related material but also insulin receptors and insulin-like growth factor I (IGF-I) receptors. Further, when embryos developed in the presence of antiinsulin antibodies, we showed retardation in both morphological and biochemical events which strongly suggested a physiological requirement for insulin in normal embryogenesis. In the present study we have evaluated the effects of insulin, proinsulin, desoctapeptide insulin, and IGF-I when applied to day 2 chick embryos. At day 4 of development biochemical indices were compared in treated vs. control groups. Insulin (10-100 ng/embryo) increased the content of protein, total creatine kinase, creatine kinase MB isozyme, triglycerides, cholesterol, phospholipids, DNA, and RNA, in a dose-dependent fashion. IGF-I had a lower potency than insulin in stimulating both metabolic and growth indices and was nearly equipotent in stimulating the creatine kinase MB content (marker of muscle differentiation). The high relative potency of insulin together with the effects of proinsulin (less than 15%) and desoctapeptide insulin (less than 10%) compared to insulin on the chick embryo, led us to infer that at low doses (nanograms per embryo) insulin stimulates developmental processes mainly through the insulin receptor, with the possible exception of muscle differentiation. The broad range of metabolic, growth, and differentiation indices stimulated by insulin and IGF-I in chick embryos, at a stage when specific receptors for both peptides are present, suggests that insulin and IGF-I may have a regulatory, complementary, or overlapping role in normal chick embryo early development.

Animals↗

Insulin antibodies retard and insulin accelerates growth and differentiation in early embryos.

The physiologic function of insulin in early embryonic life is unknown. We have shown that insulin is present in unfertilized eggs and in chick embryos at 2-3 days of development, even before the emergence of the endocrine pancreas. To define insulin's role, we exposed 2-day-old chick embryos to anti-insulin antibodies and followed their development up to day 5. Antibody-treated embryos had a higher rate of growth retardation and death by days 3-5 of embryogenesis, compared with controls. Among the survivors, biochemical maturation was delayed at days 4 and 5; weight, protein, total creatine kinase activity, and creatine kinase-MB were decreased in antibody-treated embryos. By contrast, insulin (50 ng/embryo) administered to 2-day-old embryos yielded nearly symmetrical stimulatory results. These findings suggest that endogenous insulin plays a probable physiologic role regulating growth and differentiation in early embryos. In addition, the findings provide some clues to a possible function for insulin produced outside the organism's own beta cells.

Animals↗