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Biomedical subjects

J A Rodriguez

Publications and source records attributed to J A Rodriguez.

At least 91 records · Page 5Linked to original sources

Demonstration of smoking-related DNA damage in cervical epithelium and correlation with human papillomavirus type 16, using exfoliated cervical cells.

Smoking is a known aetiological risk factor for cervical cancer. Smoking-related DNA damage (DNA adducts), in cervical epithelial cells, has recently been demonstrated to suggest a causal role in the development of cervical cancer. Human papillomavirus 16 (HPV 16) is a known oncogenic virus and is also implicated as a cause of cervical cancer. It has been suggested that both smoking and HPV may act synergistically in the development of cervical cancer. We have investigated the cervical DNA adduct level and the prevalence of HPV 16 (using polymerase chain reaction) in women who had normal cervical cytology. Both the DNA adduct assay and the HPV assay were carried out on exfoliated cervical cells recovered from cervical scrapes. In 87% of the cases there was enough DNA from the exfoliative cervical cells to analyse for DNA adducts. Smokers had higher DNA adduct levels than non-smokers (P = 0.002), confirming the previous data from cervical biopsy samples. Forty-two per cent of the specimens were found to be HPV 16 positive. There was no significant difference in smoking-related DNA damage (DNA adduct levels) between HPV-positive and HPV-negative smokers. This suggests that smoking DNA damage does not augment HPV infectivity. These results do not, therefore, support the molecular synergism theory.

Adolescent↗

Autogenous bone grafts from the femoral head for the treatment of acetabular deficiency in primary total hip arthroplasty with cement. Long-term results.

Thirty-five consecutive total hip arthroplasties in twenty-eight patients were performed with use of cement and insertion of an autogenous graft from the femoral head. Five patients (six hips) subsequently died or were lost to follow-up. The results for the remaining twenty-three patients (twenty-nine hips) were reviewed retrospectively at a mean of eleven years (range, seven to seventeen years) after the operation. All of the grafts united. The mean estimated coverage of the acetabular component by the autogenous graft was 27 per cent (range, 15 to 45 per cent). Three sockets (10 per cent) were revised because of symptomatic loosening without infection at a mean of ten years (eight, ten, and twelve years) after the index procedure. All three hips were found to have viable, bleeding bone in the region of the remaining graft. An additional eight acetabular components had a nonprogressive, asymptomatic, continuous radiolucent line at the cement-bone interface. This finding was assumed to indicate loosening of the socket, so the total prevalence of loosening was 38 per cent (eleven of twenty-nine sockets). There was no significant difference between the loose and the well fixed components in terms of the amount of coverage by the graft (p > 0.2) or the method of fixation (p > 0.4). There was no collapse or resorption of the graft that was of mechanical consequence. Autogenous femoral-head bone-grafting is a useful technique with a good potential for long-term success when the amount of coverage by the graft is limited to less than 40 per cent of the surface of the acetabular component.

Acetabulum↗

Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats.

We examined the modifying effects of CO2 on the CNS and pulmonary manifestations of hyperbaric oxygenation (HBO) in newborn rats. Four- to seven-day-old rats were exposed to HBO with inspired PCO2 (PICO2) of approximately 0, 60, 90, 140, 190, and 380 mmHg at a total pressure of 5 atm abs. The PCO2 values studied corresponded with 0, 8, 12, 18, 25, and 50 kPa, respectively, at a total pressure of 507 kPa. The O2-CO2 exposures lasted for 2-8 h. Hypercapnia at PICO2 of 60 and 90 mmHg with HBO produced extensive pulmonary damage with a high post-decompression mortality, compared to HBO alone. In contrast, PICO2 at the anesthetic levels of 140 and 190 mmHg attenuated the visible pulmonary and neurologic manifestations of O2 toxicity, and significantly reduced post-decompression mortality, compared to moderate hypercapnia of 60-90 mmHg. Supercapnia, at PICO2 of 380 mmHg, with HBO also produced no visible neurologic effect, but it caused an early apnea with severe pulmonary damage. These data indicate unique and dose-dependent cerebral and pulmonary responses to hyperoxic-hypercapnia in newborn rats. It is speculated that anesthetic levels of hypercapnia may be utilized to improve tissue oxygenation during O2 therapy in newborns, without increasing the risk of pulmonary and CNS O2 poisoning.

Animals↗

Jejunoileal bypass-induced liver dysfunction and bacterial translocation: effect of intraluminal glutamine-infusion.

We tested the effect of long-term intraluminal administration of glutamine on jejunoileal bypass (JIB) induced abnormalities in the plasma-liver profile in rats. Male Sprague Dawley rats (200-250 g) were subjected to an end to side JIB followed by daily intraluminal infusions of either 8 ml saline (n = 5), infused over a 4-hour period, or 8 ml saline containing 1g/Kg body weight glutamine (n = 7) for 3 weeks. Thirteen unoperated rats and four JIB rats without infusions served as controls. At the conclusion of the experiment, a cardiac blood sample was removed and analyzed for plasma cholesterol, albumin, total protein, gamma glutaril transferase, lactic dehydrogenase, glutamic-oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin. Tissue samples from various segments of bowel, liver, mesenteric lymph nodes, and spleen underwent histopathologic examination. Bacteriological cultures were prepared from jejunum, ileum, mesenteric lymph nodes, liver, and spleen. Bacterial translocation occurred in both JIB-saline and JIB-glutamine infused rats. Glutamine-infused rats developed a significant decrease in the plasma cholesterol levels. However, glutamine did not prevent the JIB-induced alterations in the plasma-liver profile and bowel histopathology. It is suggested that experimental JIB procedure can be used as a model of bacterial translocation consequent to mucosal permeability and intestinal inflammatory diseases.

Alanine Transaminase↗

A leucine to arginine amino acid substitution at codon 46 of rhodopsin is responsible for a severe form of autosomal dominant retinitis pigmentosa.

To evaluate the extent to which rhodopsin mutations are involved in autosomal dominant forms of retinitis pigmentosa (adRP) we collected DNAs from patients with adRP and screened the rhodopsin coding sequence with single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. This screening revealed a thymidine to guanine transversion at nucleotide 431 (nucleotide sequence numbers as per Genebank) in affected members of one family (RFS04). The nucleotide substitution leads to a missense mutation at the 46th amino acid of rhodopsin. The mutation occurs at an amino acid conserved in mammals and changes the hydrophobic nature of the protein at a transmembrane-spanning region. The mutation causes the substitution of a non-polar hydrophobic amino acid, leucine, for the basic amino acid arginine (Leu46Arg). This nucleotide substitution is unique to the family studied and occurs in the affected individuals in the family. Full-field electroretinograms (ERGs) in four affected members of the family showed nondetectable rod responses at an early age, with markedly reduced cone responses, and a faster than average rate of progression of the phenotype as measured by yearly ERGs.

Adolescent↗

[3 beta-hydroxysteroid dehydrogenase defect: frequency of presentation in a sample of Chilean hirsute women].

The defect of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) is frequent among hirsute women and clearly dependent on the ethnic composition of the studied population. Our aim was to study the frequency of 3 beta HSD deficit in a group of Chilean hirsute women. Basal and post ACTH concentrations of cortisol, 17 hydroxyprogesterone and 17 hydroxypregnenolone were measured by RIA in 40 hirsute post puberal women and in 15 normal age matched female volunteers. Criteria for considering a 3 beta HDS deficit were 17 hydroxypregnenolone values and 17 hydroxypregnenolone/17 hydroxyprogesterone and 17 hydroxypregnenolone/cortisol ratios after ACTH stimulation over the 95% confidence intervals of normal women. Basal dehydroepiandrosterone sulphate and testosterone levels were also measured in hirsute women. All samples were obtained during the follicular phase of the menstrual cycle. ACTH stimulated hormone values and ratios were diagnostic for 3 beta HDS deficit in 7.5% of hirsute women. Basal testosterone was over 80 ng/dl in 47.5% and dehydroepiandrosterone sulphate over 3.9 micrograms/ml in 52.5% of these women. There was no correlation between dehydroepiandrosterone or testosterone values and ACTH stimulated hormone values. It is concluded that 3 beta HSD is frequent in hirsute women and that its diagnosis requires the determination of ACTH stimulated 17 hydroxypregnenolone values and 17 hydroxypregnenolone/17 hydroxyprogesterone ratio.

17-alpha-Hydroxypregnenolone↗

Long-term immunogenicity and efficacy of hepatitis B vaccine in hemodialysis patients.

Although the efficacy of hepatitis B vaccines in patients under chronic hemodialysis treatment has been well documented, the persistence of immunity in this population remains largely unknown. In this study we have followed 60 hemodialysis patients up to 3 years after primary hepatitis B vaccination (four doses of recombinant hepatitis B vaccine; Engerix B, 20 mg/dose) to evaluate the persistence of immunity (as indicated by serum levels of antibody to hepatitis B surface antigen-anti-HBs-higher than or equal to 10 mIU/ml). Fourty-four (73%) patients developed anti-HBs levels above 10 mIU/ml after vaccination; the remaining 16 (27%) vaccinees were considered nonresponders and were given a booster dose that again failed to elicit an immunoresponse. After 3 years of follow-up, 18 out of 44 (41%) responders had no detectable anti-HBs levels in the serum (antibody loss occurring within 8 and 12 months in 3 cases, within 1 and 2 years in 13, and within 2 and 3 years in 2 other cases). When compared with the responders that lost their antibodies during the follow-up period, those who remained immunoreactive 3 years after vaccination was initiated were younger and had higher anti-HBs levels at 8 months of follow-up. Two hepatitis B virus infections were detected among nonresponders during the follow-up period. Based on these data, we conclude that patients undergoing chronic hemodialysis therapy not only have lower response rates to hepatitis B vaccination than healthy adults, but also that these are frequently transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Autosomal dominant sectoral retinitis pigmentosa. Two families with transversion mutation in codon 23 of rhodopsin.

A cytosine-to-adenine transversion in codon 23 of rhodopsin, the rod visual pigment gene, was reported recently by Dryja et al in 17 of 148 unrelated patients with autosomal dominant retinitis pigmentosa, but the clinical findings associated with this deletion have not been reported in detail. In screening our patients with autosomal dominant retinitis pigmentosa for the codon 23 transversion, we found positive results in four affected individuals from two families with sectoral retinitis pigmentosa, while 12 patients with sectoral retinitis pigmentosa from different families had negative results, suggesting that other gene sites or locations may give this same phenotypic change. From our patients' history of light exposure and the location of degeneration in the retina, we hypothesize that light phototoxicity may be playing an expressive role in this point mutation of the rhodopsin gene. This is the first report in which a type of retinitis pigmentosa has been associated with a specific molecular gene defect, although the actual pathophysiologic mechanism currently is unknown.

Adult↗

Acute effect of systemic versus intracoronary dipyridamole on coronary circulation.

Dipyridamole has been proposed as an ideal agent to evaluate coronary vascular reserve because it produces selective coronary vasodilation without systemic hemodynamic effect. The actions of intracoronary (IC) and intravenous (IV) dipyridamole on coronary blood flow and systemic hemodynamics were compared in 15 patients with chest pain syndrome and normal coronary arteries. They received IC dipyridamole, followed 10 minutes later by 0.5 mg/kg of IV dipyridamole. IC dipyridamole produced a 73% increase in coronary sinus flow without hemodynamic changes, except for a slight increase in pulmonary systolic and diastolic pressures. IV dipyridamole administration produced an additional 88% increase in coronary sinus flow, reaching 172% over baseline; it was also associated with a significant (p less than 0.01) increase in heart rate (78 +/- 14 vs 102 +/- 19 beats/min), cardiac index (4 +/- 0.7 vs 6.3 +/- 1.7 liters/min/m2), and pulmonary artery systolic (27 +/- 5 vs 34 +/- 7 mm Hg) and diastolic pressures (12 +/- 4 vs 19 +/- 7 mm Hg). These data suggest that the coronary vasodilatory effect seen after IV dipyridamole administration is related to mechanisms other than direct coronary vasodilation.

Adult↗

Increased excretion of kallikrein during dexamethasone administration in normal man on low and normal salt intake.

The effect of dexamethasone administration for 3 days on urinary kallikrein excretion was studied in 12 normal men with normal sodium intake (n = 6) or low sodium intake (n = 6). Urinary excretion of sodium, potassium, 17-hydroxycorticosteroids, aldosterone and water was also measured in all subjects. Dexamethasone administration was associated with a significant increase in urinary kallikrein excretion (F3, 30 = 6.9; P less than 0.001) regardless of sodium intake. No significant correlation could be established between the increase in urinary kallikrein excretion and changes in urinary sodium, potassium, 17-hydroxycorticosteroids, aldosterone or water. These results suggest that dexamethasone can exert a direct action on the renal kallikrein-kinin system.

17-Hydroxycorticosteroids↗

beta-Fucosidase, beta-glucosidase and beta-galactosidase activities associated in bovine liver.

1. beta-D-Fucosidase, beta-D-glucosidase and beta-D-galactosidase activities from bovine liver are associated in a single peak in isoelectric focusing. The isoelectric point is 4.35 for all these activities, suggesting that they are catalyzed by the same enzyme. 2. This enzyme shows the optimal pH in the range 4.5-6.5 for all the above mentioned activities. 3. The Km and Vmax are 0.26 mM and 31 mU mg-1, 0.10 mM and 24 mU mg-1, and 0.30 mM and 20 mM mg-1 for the p-nitrophenyl-fucoside, -glucoside and -galactoside, respectively. The glucoside derivative is the best substrate, with a Vmax/Km value of 0.24 ml . mg-1 . min-1. 4. The Lineweaver-Burk profiles are convex upward in most cases, suggesting a substrate-activation model, and the presence of more than one binding site in the enzyme. 5. The Ki for all the activities were determined with D-fucose, glucose and galactose as inhibitors. D-Fucose is the strongest inhibitor. The inhibition is competitive in all cases.

Animals↗

Bartter's syndrome.

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Acidosis, Renal Tubular↗

Abnormal regional myocardial flow in myocardial bridging of the left anterior descending coronary artery.

A patient with angina pectoris, myocardial bridging of the left anterior descending coronary artery and otherwise normal coronary arteries is presented. Regional myocardial blood flow was studied with the thermodilution technique. Atrial pacing of the heart at a rate of over 140/min reproduced the anginal syndrome, with S-T segment depression in the electrocardiogram. There was a transient decrease in great cardiac vein flow during rapid pacing with a simultaneous increase in total coronary sinus flow. The study demonstrates that in this patient, a myocardial bridge was associated with decreased blood flow to the area perfused by the bridged artery with a concomitant increase in coronary sinus flow as the pacing rate was increased from 96 to 150 and 180/min. After administration of nitroglycerin, the bridging effect was more accentuated on angiography; pacing-induced tachycardia was associated with similar changes in great cardiac vein and coronary sinus flows with less S-T segment depression in the electrocardiogram and chest pain of milder intensity.

Angina Pectoris↗

The effect of vasopressin in water-loaded hypokalemic patients is prostaglandin-independent.

Potassium-depleted subjects regularly excrete dilute urine with a high free-water clearance which cannot be suppressed either by solute loading or by water deprivation. In man, as in the dog and rat, potassium depletion impairs the ability of the kidney to achieve maximal urinary solute concentration and vasopressin is unsuccessful in overcoming this defect. In man and in the dog, potassium depletion induces a rise in urinary prostaglandin E2, an effect which can be reversed with indomethacin, a cyclo-oxygenase inhibitor. To evaluate the role of prostaglandins on the renal action of vasopressin in hypokalemia, six subjects with hypokalemia of various etiologies were studied in a control, drug-free condition and again after 3 to 6 days of indomethacin (100 mg/day). Renal clearance studies to measure the maximal free-water excretion in response to an intravenous water load (10 ml/min) and to a superimposed infusion of arginine vasopressin (40 mU/hr) were performed. The results in six patients are as follows: maximal free-water clearance (control) 8.03 +/- 0.8 ml/min (mean +/- S.E.), with the addition of vasopressin, .14 +/- 0.8; after 3 to 6 days of indomethacin, 8.55 +/- 1.33; with vasopressin 0.91 +/- 1.23 ml/min. There was no statistically significant difference between the maximal free water clearance with or without indomethacin. Vasopressin exerted an equally great response in both conditions and prostaglandins did not appear to play a role in free-water formation.

Adult↗

Effect of a calcium inhibitor, nifedipine, on exercise tolerance in patients with angina pectoris: a double-blind study.

The effect of nifedipine on exercise tolerance was studied in 30 patients with stable angina and positive graded exercise testing. Treadmill exercise testing was performed on each of five consecutive days. Placebo or nifedipine, 10 mg sublingually, was given 30 minutes before exercise on the third day. The following day the intervention was reversed in a double-blind manner. Angina was abolished by nifedipine but not by placebo in 12 patients (40 percent). The time to onset of angina in the remaining patients increased from 4.1 +/- 0.4 (SEM) to 6.7 +/- 0.6 min (p less than .001). Time to ST depression greater than or equal to 2 mm increased from 4.0 +/- 0.3 to 5.4 +/- 0.5 min, while duration of exercise increased from 6.3 +/- 0.3 to 8.2 +/- 0.4 min (p less than .001). The maximum heart rate was 145 +/- 3.3 with nifedipine and 122 +/- 3.8 min-1 with placebo (p less than .01). Resting systolic blood pressure decreased 30 min after nifedipine administration from 131 +/- 3.4 to 106 +/- 2.9 mm Hg (p less than .01). Maximal systolic blood pressure during exercise was lower with nifedipine (127 +/- 4.8 mm Hg) than with placebo (155 +/- 5.6 mm Hg, p less than .01). We conclude that nifedipine significantly improves the exercise tolerance of patients with stable angina pectoris by decreasing peripheral vascular resistance and myocardial oxygen demand.

Adult↗