Monitoring adherence to HIV therapy.
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Adult↗
Biomedical subjects
R Paredes
Publications and source records attributed to R Paredes.
Germline origins in the human F9 gene: frequent G:C-->A:T mosaicism and increased mutations with advanced maternal age.
The factor IX gene (F9) is an advantageous system for analyzing recent spontaneous germline mutation in humans. Herein, the male:female ratio of mutation ("r") in F9 have been estimated by Bayesian analysis from 59 germline origin families. The overall "r" in F9 was estimated at 3.75. The "r"s varied with the type of mutation. The "r"s ranged from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (>1 kb), respectively. The "r" for the two subtypes of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 origin individuals for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately one part in 20). Four of the five defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 US Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen. However, an advanced maternal age effect was observed (P=0.03) and was particularly prominent for transversions (average of the 79th percentile when maternal age was normalized for the year of conception). This suggests that an increased maternal age results in a higher rate of transmitted mutation, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation.
Adolescent↗
Validation of logistic regression models in small samples: application to calvarial lesions diagnosis.
We have used the leave-one-out (LOO) method and the area under the receiver operating characteristic (ROC) curve to validate logistic models with a sample of 167 patients with calvarial lesions. Seven logistic regression models were developed from 12 clinical and radiological variables to predict the most common diagnoses separately. The LOO method was used to test the validity of the equations. The discriminant power of every model was assessed by means of the area under the ROC curve (Az). The model with the greatest discrimination ability for the whole data set was the osteoma equation (Az = 0.951). The discriminatory ability of the statistical models decreased significantly with the LOO procedure, having the malignancy model the highest value (Az = 0.931). The LOO method can obtain a high benefit from small samples in order to validate prediction rules. In studies with small samples, resampling techniques such as the LOO should be routinely used in predictive modeling. This method may improve the forecast of infrequent diseases, such as calvarial lesions.
Bone Neoplasms↗
Benefit of switching from a protease inhibitor (PI) to nevirapine in PI-experienced patients suffering acquired HIV-related lipodystrophy syndrome (AHL): interim analysis at 3 months of follow-up.
This multicentre, randomized, open-label, prospective trial is evaluating the effects of switching treatment from a protease inhibitor (PI)-containing regimen to one containing the non-nucleoside reverse transcriptase (RT) inhibitor nevirapine in human immunodeficiency virus (HIV)-infected patients with durable viral suppression but suffering from lipodystrophy. Objectives of this ongoing study are to evaluate the effects of this switch on changes in body shape and metabolic abnormalities associated with acquired HIV-related lipodystrophy syndrome (AHL), as well as on maintenance of viral suppression and immunological and psychological effects. Preliminary data involving 57 patients with 3 months of follow-up show an initial improvement of AHL in two regions, the face and arms. There is also a tendency toward improved cholesterol and triglyceride levels and improved quality of life among patients receiving the nevirapine-containing regimen. Maintenance of viral suppression was equivalent in both treatment groups. Additional data with longer follow-up are needed to confirm these results.
Adult↗
Quebrada jaguay: early south american maritime adaptations
Excavations at Quebrada Jaguay 280 (QJ-280) (16 degrees30'S) in south coastal Peru demonstrated that Paleoindian-age people of the Terminal Pleistocene (about 11,100 to 10,000 carbon-14 years before the present or about 13,000 to 11,000 calibrated years before the present) in South America relied on marine resources while resident on the coast, which extends the South American record of maritime exploitation by a millennium. This site supports recent evidence that Paleoindian-age people had diverse subsistence systems. The presence of obsidian at QJ-280 shows that the inhabitants had contact with the adjacent Andean highlands during the Terminal Pleistocene.
Journal Article↗
Calvarial eosinophilic granuloma: diagnostic models and image feature selection with a neural network.
RATIONALE AND OBJECTIVES: The authors analyzed the accuracy of diagnostic features used by an artificial neural network compared with logistic-regression analysis in the diagnosis with computed tomography (CT) of calvarial eosinophilic granuloma. MATERIALS AND METHODS: Thirty-one of 167 patients with calvarial lesions were found to have eosinophilic granuloma. Clinical and CT data were used for logistic-regression and neural network models. Both models were tested by using the leave-one-out method. The final results of each model were compared by means of the area under the receiver operating characteristic curve (Az). RESULTS: Identification of eosinophilic granuloma was significantly more accurate with the neural network than with logistic regression (Az = 0.9846 +/- 0.0157 [standard deviation] vs 0.9117 +/- 0.0373) (P = .001). The most important diagnostic features identified with the neural network were patient age and marginal sclerosis. For logistic regression, the most important features were age, shape, and lobularity. CONCLUSION: The neural network is a useful tool for analyzing the features of calvarial eosinophilic granuloma. Age and marginal sclerosis are important diagnostic features.
Adolescent↗
Focal calvarial bone lesions. Comparison of logistic regression and neural network models.
RATIONALE AND OBJECTIVES: To assess the accuracy of logistic regression (LR) and artificial neural networks (NN) in the diagnosis of calvarial lesions using computed tomography (CT) and to establish the importance of the different features needed for the diagnosis. METHODS: One hundred sixty-seven patients with calvarial lesions as the only known disease were enrolled. The clinical and CT data were used for LR and NN models. Both models were tested with the leave-one-out method. The final results of each model were compared using the area under receiver operating characteristic curves (Az). RESULTS: Of the lesions, 73.1%, were benign and 26.9% were malignant. There was no statistically significant difference between LR and NN in differentiating malignancy. In characterizing the histologic diagnoses, NN was statistically superior to LR. Important NN features needed for malignancy classification were age and edge definition, and for the histologic diagnoses matrix, marginal sclerosis, and age. CONCLUSION: NNs offer wide possibilities over statistics for the study of calvarial lesions other than their superior diagnostic performance.
Adolescent↗
Leishmaniasis in HIV-infected persons: a review.
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AIDS-Related Opportunistic Infections↗
Two novel factor IX promoter mutations: incremental progress towards 'saturation in vivo mutagenesis' of a human promoter region.
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Base Sequence↗
Molecular epidemiology of factor IX germline mutations in Mexican Hispanics: pattern of mutation and potential founder effects.
Germline mutations in patients with hemophilia B generally have arisen within the past 150 years. Evidence suggests that these germline mutations generally result from endogenous processes. However, a unique pattern would be expected if a population were exposed to a physiologically important germline mutagen since mutagens generally produce characteristic patterns, or "fingerprints", of mutation. To determine the pattern of mutation in Mexican Hispanics, the regions of likely functional significance in the factor IX gene were screened by dideoxy fingerprinting (ddF) in 31 families with hemophilia B. Mutations were found in 30 of these families. Haplotype analysis was performed on individuals with identical mutations to help distinguish independent, recurrent mutations from founder effects. Analysis of these 30 mutations, along with 7 mutations reported previously in Mexican Hispanic families, reveals a pattern of independent mutation that is similar to the pattern of mutation observed in 127 U.S. Caucasian families (p = 0.89). These results may reflect either an underlying pattern of germline mutation due to endogenous processes or the presence of an ubiquitous mutagen. Further analyses of the recurrent mutations revealed that two mutations, T296M and R248Q, accounted for 19% of the mutations found in the Mexicans. Haplotype data suggest that the multiple occurrences of T296M and R248Q are associated with founder effects and that screening for these mutations may allow rapid mutation detection and carrier diagnosis in a significant minority of Mexican families with hemophilia B, These two mutations also are associated with founder effects in the U.S, Caucasian population. However, the haplotypes are different in these two populations, indicating independent origins. The occurrence of identical founder mutations in distinct populations provides evidence for the previous hypothesis that the number of different mutations giving rise to mild or borderline mild/moderate hemophilia B is small compared to deleterious mutations causing more severe disease.
Factor IX↗
[Association between post-initial remission and HLA phenotype in Type I diabetics].
Our goal was to estimate the occurrence rate of the post-initial remission and its relation with HLA phenotype in type I diabetics (DMI). We studied 50 type I diabetics, 22 women and 28 men, with an average age at the onset of the disease to 15.8 +/- years (range 3-30 years). All patients were conventionally treated with insulin therapy, diet and regular exercise. Six (12%) of the diabetics presented a complete remission during 57.3 +/- 46 weeks, whereas fifteen (30%) patients presented partial remission during 20.1 +/- weeks. No significant differences were observed with regard to age at the onset of the disease, sex, BMI, initial ketoacidosis and stage of gonadal development between those diabetics presenting remission and those who did not presented so. We observed a higher incidence of the HLA-DR4 antigen among diabetics with remission (complete and partial, 61.9%), compared with patients without remission (20%, p less than 0.5). In conclusion, our results support the findings suggesting the presence of a clinical-immunological heterogenicity in DMI, genetically determined and linked to the HLA system.
Adolescent↗
Sexual behavior and copulatory thrusting patterns in male rabbits treated with GABA transaminase inhibitors.
The effects of enhanced central nervous system GABA levels on sexual behavior and copulatory pelvic thrusting were evaluated in male New Zealand white rabbits. The GABA transaminase inhibitors sodium valproate and gamma-acetylen GABA (GAG), in doses of 100 and 200 mg/kg and 50 and 100 mg/kg, respectively, were intraperitoneally administered and sexual behavior recorded at several intervals after drug administration. At the same time, copulatory thrusting was registered using a polygraphic technique. Tests for gross motor functions were also performed. None of the drugs had any effect in these latter tests. Sodium valproate, in a dose of 100 mg/kg, had a slight inhibitory effect on sexual behavior at 280 min postinjection. A dose of 200 mg/kg inhibited sexual activity already 15 min postinjection, and the effect lasted for at least 280 min. GAG, 100 mg/k, inhibited mounting behavior at 8 h postinjection, and ejaculation was reduced from 2 to at least 8 h postinjection. Copulatory thrusting patterns were not affected by the drug treatments. These data suggest that increased GABAergic activity reduces sexual arousal in the rabbit. GABA does not seem to be critically involved in the regulation of the motor patterns underlying pelvic thrusting. There are important quantitative and qualitative differences between rats and rabbits with regard to the actions of GABA transaminase inhibitors upon sexual functions.
4-Aminobutyrate Transaminase↗
Medial preoptic area kindling induces sexual behavior in sexually inactive male rats.
In the present experiments, sexually experienced and non-copulating male rats were kindled in the medial preoptic area (MPOA) or the amygdala (AMG) with the purpose to investigate if the widespread modification of brain function produced by kindling induces sexual behavior in non-copulating rats and if kindling facilitates sexual behavior in copulating rats. Since kindling in the MPOA has been little studied, a description of this phenomenon is also presented. The animals were stimulated 4 times daily on odd days and sexual behavior monitored on even days. The results showed that the MPOA required higher stimulus intensity to elicit an afterdischarge (AD) than the AMG. The AD duration was significantly longer in animals kindled in the MPOA than in animals kindled in the AMG. No difference was found in the development of kindling between these brain structures. Kindling had no effect upon sexual behavior in copulating rats. In contrast, MPOA kindling induced copulation in non-copulating male rats. Seven out of 9 animals displayed sexual behavior. No significant facilitation was observed after AMG kindling in non-copulating male rats. Furthermore, the sexual behavior displayed by the previously non-copulating MPOA kindled rats was similar to the sexual behavior displayed by sexually experienced animals. It is proposed that sexual behavior is facilitated in these male rats by local neural changes produced by kindling.
Animals↗
[Tuberculosis in kidney transplant patients].
We studied the incidence of tuberculosis in 37 renal transplant patients. Mean age was 37 years and immune suppression therapy had been used for a mean of 37 months. Tuberculosis-free cases had received prednisone at a mean dose of 10 +/- 4 mg/day and azathioprine, 96 +/- 35 mg/day. 28% of patients had a positive tuberculin test, 24% a healed tuberculous lung lesion and 40% received chemoprophylaxis. Four patients developed tuberculosis, 10 times the incidence expected for the general population. Fever was present in all patients. Two patients had a disseminated form and one a laryngeal location. None of the patients had received chemoprophylaxis and the dose of prednisone was higher (18 +/- 9 mg/day) than that received by non-infected patients. Thus, chemoprophylaxis for tuberculosis appears warranted in all renal transplant recipients, regardless of tuberculin test results or chest X ray findings.
Adult↗
Stereospecific actions of baclofen on sociosexual behavior, locomotor activity and motor execution.
The behavior effects of racemic baclofen and the R and S enantiomers were studied in order to determine whether the stereospecificity found in receptor binding studies also applies to the behavioral actions of the drug. Racemic and R-baclofen inhibited sexual behavior, locomotor activity and motor execution at relatively low doses while s-baclofen was completely inactive even when a dose 40 times higher than the minimum effective dose of R-baclofen was used. The R enantiomer seems to be twice as active as racemic baclofen. These data strongly suggest that the behavioral effects of baclofen are the result of an action at the GABA-B receptor. In order to differentiate the effects of baclofen on sexual interactions from those on nonspecific social interactions, the sociosexual behavior was observed with a castrated male or a receptive female as stimulus animal. R, S-baclofen had effects only upon sociosexual interaction with a receptive female. Moreover, the inhibitory effects of baclofen were restricted to behavioral items related to sexual interactions, primarily those constituting precopulatory behaviors. Since no effect was observed in social interactions with a castrated male, it is suggested that the inhibition of sociosexual behavior is not a consequence of impairment of motor execution. Rather it appears that baclofen has a specific inhibitory effect on behaviors associated with the initiation of copulatory activity. Therefore, once initiated, sexual behavior was not significantly modified by baclofen.
Animals↗
GABAergic drugs and lordosis behavior in the female rat.
Agents modifying GABAergic neurotransmission were administered to ovariectomized rats treated with different doses of estradiol benzoate (EB) + progesterone (P) or with EB alone. Hormone treatments were designed to induce an intermediate level of receptivity in order to be able to observe both stimulatory and inhibitory effects on lordosis behavior. Both the GABAA receptor agonist THIP and the GABAB receptor agonist baclofen inhibited lordosis behavior at doses from 20 and 5 mg/kg, respectively. The GABA transaminase inhibitor gamma-acetylen GABA (GAG) and the GABA agonist 3-aminopropanesulfonic acid had no effects, even when high doses were administered. The GABAA receptor antagonist bicuculline had no effect by itself nor did it block the effects of THIP. It is therefore suggested that the GABAA receptor is of slight importance in the control of lordosis behavior. No evidence could be found supporting the hypothesis that an interaction between P and GABA is important for hormone-induced receptivity. It does not appear likely that motor disturbances are responsible for the inhibitory effects of baclofen and THIP. The exact mechanism by which these drugs inhibit lordosis behavior is not clear at present.
Alkynes↗
[Adenosine deaminase activity in peritoneal tuberculosis].
We performed a prospective study including cytochemical, bacteriologic and pathologic observations in 25 patients with ascites of different causes. Activity of adenosine deaminase in ascitic fluid was higher in tuberculous (103 +/- 61 mu/l) than in neoplastic (16 +/- 8), inflammatory (16 +/- 13) and portal hypertension (15 +/- 6) etiologies (p less than 0.05). Inflammatory cases included patients with lupus and spontaneous peritonitis. Activity of adenosine deaminase was higher in every patient with tuberculosis than in any other patient. Thus, a high sensitivity and specificity of this test in the diagnosis of tuberculous peritonitis is confirmed.
Adenosine Deaminase↗
Opioids and sexual behavior in the male rat.
Naloxone in the doses of 4 or 16 mg/kg failed to affect copulatory behavior of testosterone-treated castrated male rats. Morphine 10 mg/kg, administered 60 min before behavioral observation, reduced the proportion of animals displaying sexual behavior. Doses of 2.5 or 5 mg/kg reduced the latency to the second ejaculation, whereas the few animals still copulating after morphine 10 mg/kg showed a reduced latency to the first ejaculation. The same doses of morphine administered 5 min before behavioral observation produced a dose-dependent reduction of mount, intromission and ejaculation percentages. However, those animals that did copulate showed a normal copulatory behavior. D-Ala2-Met5 enkephalinamide (DALA) infused into the left cerebral ventricle in a dose of 5 micrograms 5 or 60 min before tests had no effect. When the peptide was infused 30 sec after the first intromission, the number of intromissions as well as the latency to ejaculation were reduced. Opioids may facilitate ejaculatory mechanisms, perhaps as a consequence of their rewarding properties. Moreover, in animals treated with DALA after the first intromission, the number of intromissions and the latency to ejaculation were similar for the first and second copulatory series, while these parameters were much reduced upon the second ejaculation for control animals. It is possible that liberation of endogenous opioids is the cause of ejaculation-induced facilitation of subsequent sexual behavior.
Animals↗