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Biomedical subjects

F Alvarez

Publications and source records attributed to F Alvarez.

At least 73 records · Page 4Linked to original sources

Contraception with two levonorgestrel rod implants. A 5-year study in the United States and Dominican Republic.

A 5-year trial of a two-rod contraceptive implant, which releases the progestin levonorgestrel (LNG rod), was conducted at four clinics with 594 women. Mean age and weight at admission were 25.5 years and 62.4 kg, respectively. Consent to continue through 5 years was sought and obtained when the 3-year cumulative pregnancy rate proved to be 0.8 per 100. No pregnancies occurred in the fourth or fifth years. The 5-year cumulative pregnancy rate was, therefore, 0.8 per 100 with an annual average pregnancy rate below 2 per 1000 women. Prolonged bleeding/spotting (8.2% of subjects) and irregular bleeding (5.6%) were the most frequently cited medical reasons for removal. Removals for headache (4.7%) and weight change (4.0%) were the next most frequent medical reasons. Between 1% and 2% of subjects during the 5-year trial sought removals for each of the following conditions: mood changes, lower abdominal pain, depression, or pain at the implant site. The mean annual continuation rate during the study was 77 per 100. Use per woman averaged 2.96 years. Mean removal time was 5.9 +/- 0.6 min. These data indicate that, for a 5-year period, the two LNG rod implants are equivalent to the six Norplant capsule implants with respect to safety and efficacy parameters, but permit easier and more rapid implant removal.

Adolescent↗

Timing of onset of contraceptive effectiveness in Norplant implant users. Part I. Changes in cervical mucus.

OBJECTIVE: To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinics. PATIENT(S): Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study. INTERVENTION(S): Cervical mucus and blood samples were obtained. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel. RESULT(S): The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration. CONCLUSION(S): On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.

Adult↗

Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial.

BACKGROUND & AIMS: Treatment of chronic hepatitis B with interferon alfa is not approved in children. The aim of this study was to evaluate the safety and efficacy of interferon alfa (IFN-alpha) in children with chronic hepatitis B and increased transaminase levels. METHODS: Children were given either IFN-alpha2b (6 megaunits/m2 thrice weekly for 24 weeks) or no treatment. Clearance of markers of viral replication was evaluated 24 weeks after therapy and after 48 weeks of observation in controls. RESULTS: Of 149 children enrolled, 144 were evaluable (70 treated and 74 controls). Serum hepatitis B e antigen and viral DNA became negative in 26% of treated children and 11% of controls (P < 0.05). Serum aminotransferase levels normalized and liver histology improved among responders. Hepatitis B surface antigen became undetectable in 10% of treated patients and 1% of controls. Female gender and interferon treatment were the only significant predictors of response. Ethnic origin, baseline aminotransferase level, initial DNA levels, and histology did not correlate with response. Most adverse reactions were mild or moderate, and dose was reduced in 24% of children. CONCLUSIONS: In children with chronic hepatitis B, INF-alpha promotes loss of viral replication markers and surface antigen and improves aminotransferases and histology.

Adolescent↗

MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis.

BACKGROUND/AIMS: Autoimmune hepatitis has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group. The aim of this study was to analyse the immunogenetics of type I autoimmune hepatitis in Mexicans. METHODS: Thirty Mexican Mestizo patients and 175 healthy controls were HLA typed as follows: class I antigens were determined by microlymphocytotoxicity and class II typing was done on DNA samples using PCR-SSO and PCR-SSP for DRB1, DQA1 and DQB1 loci. RESULTS: A significant association of autoimmune hepatitis with DRB1*0404 was found, (chi2Y=19.95, pc=0.002, RR=7.71), suggesting the presence of a susceptibility gene located at the DRB1 locus. Resistance was at least partially due to a DQB1 gene, since a significant decrease in DQB1*0301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB1*0404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (chi2Y=5.12, p=0.02) was increased in the early onset group. CONCLUSIONS: The possible mechanism of HLA association is due to "shared epitopes", since DRB1*0404, and those found in other populations namely, DRB1*0401, *0405 and *0301 share almost the same sequence at position 67-72 (LLEQRR, R or K at 71). Valine-86 is also relevant to the age at onset because DRB1*0404 is increased in the patients with an average age at onset of 32. These findings are relevant in determining which peptides in the liver are targets for T cells.

Adult↗

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats.

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.

Animals↗

Study of antigenic sites on the asialoglycoprotein receptor recognized by autoantibodies.

The aim of this study was to identify the epitopes recognized by antibodies to the asialoglycoprotein receptor, a specific hepatocyte protein, from sera of patients with autoimmune hepatitis. An ELISA test was used to detect anti-asialoglycoprotein receptor antibodies in the sera of patients with autoimmune hepatitis. Positive sera were tested against the same antigen by slot blot, by Western blot and by immunoprecipitation of the untreated protein and following treatment with beta-mercaptoethanol (beta-ME) and endoglycosidase F. The mature, unglycosylated and partially glycosylated forms of the asialoglycoprotein receptor synthesized by HepG2 cells were tested against positive patients' sera, as well as the in vitro translated unglycosylated form of the H1 subunit of the receptor. Sera from patients with autoimmune hepatitis recognized equally the native form, as well as the beta-ME-modified form, but less well the deglycosylated form of the human mature receptor. No reactivity was found when these sera were tested against the denatured human protein. In addition, neither the unglycosylated H1 subunit nor any of the HepG2-synthesized asialoglycoprotein receptor forms bound to the antibodies. Altogether, these results show that anti-asialoglycoprotein receptor antibodies in the sera of patients with autoimmune hepatitis are directed against conformational structures of the mature hetero-oligomeric form of the human liver protein and that at least some epitopes were located on the extracellular domain of the antigen.

Asialoglycoprotein Receptor↗

Endometrial thickness and oestradiol concentration in women with bleeding complaints during use of Norplant implants.

The objective of this study was to measure oestradiol, progesterone and endometrial development among Norplant implant users with bleeding complaints. Seventy-six volunteers complaining of prolonged/frequent bleeding were enrolled. Oestradiol, progesterone and endometrial thickness (assessed by vaginal ultrasound) were determined at that visit. Two thirds of the women had low oestradiol (< 50 pg/ml) and all except one had low progesterone concentrations (< 3 ng/ml). A total of 68% had a very thin endometrium (< 3 mm). A subgroup of 21 women were followed twice a week for 8 consecutive weeks. Oestradiol and progesterone concentrations remained low during the continuous bleeding episodes or short bleeding-free intervals (< or = 15 days), yet increased five- to sixfold (253.4 +/- 142.2 pg/ml) in long bleeding-free intervals. Endometrial thickness remained thin irrespective of the differences in bleeding patterns and oestradiol. We conclude that Norplant implant users with bleeding complaints are usually characterized by low oestradiol concentrations, absence of luteal activity and thin endometrium. A good correlation exists with increasing oestradiol concentrations and longer bleeding-free intervals, but this is not manifested by increased endometrial thickness. However, few subjects bleed with relatively high oestradiol concentrations, therefore a better understanding of the intimate disturbances related to endometrial bleeding in users of long-acting progestins is still pending.

Contraceptive Agents, Female↗

[Prenatal diagnosis. II. Importance of ultrasonographic markers in prenatal diagnosis of chromosome abnormalities].

The Medical Genetic Unit of the University of Zulia (MGUUZ) has developed a Prenatal Diagnosis Program (PDP) since January-1993, in which Genetic Risk Factors are determined in couples who request prenatal genetic counseling. In this program, different prenatal diagnostic procedures are performed to detect congenital defects during intrauterine life. One of these procedures is the Fetal Sonogram (FS). FS is a non invasive technique which permits the prenatal diagnosis of many genetic dysmorphic syndromes. Through the search of abnormal specific characteristics in the fetus, chromosomopathies may be suspected. These findings are named "Echosonographic Markers of Chromosomal Abnormalities" (EMCA). During three years (January-1993 to December-1996), patients attended in the PDP included 321 pregnant women in which 312 FS were performed. Abnormal outcomes were 22 (17 with isolated congenital malformations and 5 with EMCA). Only one fetus with chromosome abnormality (46,XX21q-) could not be detected by FS. The goals of this paper are: 1) to report 5 patients with sonographic markers suggestive of chromosomal abnormalities and 2) to show the FS usefulness in prenatal diagnosis of chromosompathies. We conclude that, in the search of the EMCA the FS should be offered systematically to all pregnant women without recognizable genetic risk. They are the main group with optimal reproductive age and in consequence, with the possibility of having a relatively major number of conception outcomes with congenital defects, with or without chromosomic etiology. The majority of those defects can be detected by FS and could allow us to select the patients in which the use of an invasive prenatal diagnostic procedure could be justified.

Adolescent↗

[Contents of various nutrients, minerals and seasonal fluctuations in Porphyra columbina, an edible marine algae from the Argentine Patagonian++ coast].

Porphyra columbina (Rodophyta Bangiales), one of the most important edible seaweeds, grows abundantly in the southern Argentine coast. Their mineral content and seasonal fluctuations were determined because there is no national data about their nutritional value. Samples were collected from April 1993 to February 1994 from Golfo San Jorge (30 Km South of Comodoro Rivadavia). Algae were washed with sea water and dried at room temperature (20-2 degrees C) for 24 hs, following the local processing procedure. Moisture and ashes were determined according to A.O.A.C. After mineralization with nitric acid sodium and potassium were determined by flame photometry; calcium, magnesium and iron by atomic absorption spectrophotometry (AAS); and phosphorus by Gomori's method. The results, expressed per 100 g dry algae showed the following values: moisture content: 7.03 to 11.00 g/100 g; ashes: 16.18 to 22.70 g/100 g; sodium: 3.18 to 6.41 g/100 g; potassium 1.24 to 1.96 g/100 g; magnesium: 600 to 836 mg/100 g; phosphorus: 78 to 276 mg/100 g; calcium: 63 to 108 mg/100 g and iron: 3.9 to 26.4 mg/100 g. The results of composition of algae as manufactured in the region showed important seasonal differences, with the highest values of ashes, sodium, potassium and magnesium in winter season (June and July).

Argentina↗

Acute intrahepatic portal vein thrombosis complicating cholangitis in biliary atresia.

UNLABELLED: A 2-year-old boy with Kasai portoenterostomy had systemic features suggestive of cholangitis and acute portal vein obstruction. The rapid rise in portal pressure caused a transient, severe decompensation of hepatic function. A superior mesenteric arterial angiogram confirmed the presence of diffuse intrahepatic portal vein thrombosis. CONCLUSION: This case provides clinical and radiological evidence supporting an association between ascending cholangitis and acute intrahepatic portal vein thrombosis.

Biliary Atresia↗

Single neuron model with recurrent excitation: response to slow periodic modulation.

The influence of a recurrent excitatory connection on the response of three neuron models to slow periodic modulation is analyzed. The models are the graded response model and the threshold model with and without adaptation. Lissajous displays of the system's output (discharge rate) as a function of the instantaneous input value show hysteresis in all three models. Hence, the outputs are different depending on whether the input is increasing or decreasing. Recurrent excitation increases the width of the hysteresis with (i) the frequency of the periodic modulation, (ii) the transmission delay of the recurrent connection, and (iii) the connection strength.

Action Potentials↗

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Adolescent↗

Contraceptives for lactating women: a comparative trial of a progesterone-releasing vaginal ring and the copper T 380A IUD.

From approximately one week before normal ovulation resumes, lactating women require protection against pregnancy by a contraceptive that is safe for both infant and mother in a multicenter one-year study, the natural hormone, progesterone, delivered vaginally by a sequence of four contraceptive rings designed for continuous use, was evaluated as a contraceptive for nursing mothers in comparison with the Copper T 380A IUD. Individual rings release in effective average dose of 10 mg day for a 3 month period. Evaluation included measures of lactational performance as well as of contraceptive efficacy and safety to mother and child. Nine participating clinics enrolled 802 ring users and 734 IUD acceptors between postpartum days 29 and 63. Life table analyses were performed with parallel decrements for ring and IUD subjects. Continuation in the study and analysis required that subjects not stop breastfeeding. The ring, with a one-year pregnancy rate of 1.5 per 100, did not differ significantly from the IUD with respect to contraceptive effectiveness (p > 0.05). More than half of the ring subjects were continuing at 6 months post admission and a quarter (23.5 per hundred) were still using the ring and breastfeeding one year after admission. Women with the IUD, however, had higher continuation rates (p < 0.001) at both time points. The largest single decrement for each method was that for weaning. Ring users had more complaints of vaginal problems but had fewer vaginal disorders on examination. At 12 months postpartum, 46 per 100 continuing ring users remained in amenorrhea. Lactation performance and the health and weight gain of the infants were similar among users of either regimen.

Administration, Intravaginal↗

First week drug concentrations in women with levonorgestrel rod or Norplant capsule implants.

Forty-two healthy women volunteered to have blood samples drawn at 2, 4, 8, 24, 48, and 168 h (7 days) following placement of levonorgestrel-releasing rod (LNG rod) or of Norplant capsule implants to permit measurement of drug concentrations. Three clinics recruited 10 women each, half of whom used each type of implant. Twelve additional subjects were later enrolled at one site to provide greater detail for the capsule implants. Throughout the week, women with Norplant implants had apparently higher mean drug concentrations than did women with LNG rod implants, but the differences were significant only in the first 48 h after placement (p < 0.05). Maximum levels for capsule implants were found at the 24-h sample (mean, 1358 to 1474 pg/mL) and for the LNG rod implants at 48 h (772 pg/mL). Body weight was negatively correlated with levonorgestrel concentrations at all times (p < 0.05). For several sampling times, differences between clinics in mean concentrations were statistically significant after weight adjustment. Despite differences by implant type, weight, or clinic location, drug concentrations compatible with contraceptive effect were attained within 24 h in users of LNG rod or of Norplant implants, insofar as all women had levonorgestrel concentrations above 250 pg/mL at the 24-h sample.

Adolescent↗

Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan.

There is an urgent need to develop safe, effective, and acceptable vaginal products for the prevention of sexually transmitted infections. Preliminary in vitro results suggest that vaginal formulations of sulfated polysaccharides, including iota-carrageenan, have the potential to block mucosal transmission of human immunodeficiency virus (HIV). Twenty-five women in five sites participated in Phase I trials to evaluate the safety of a formulation containing iota-carrageenan (PC 213). The results of this study indicate that a 5 mL 2% gel formulation of iota-carrageenan is not associated with significant irritation of the female reproductive tract when administered once daily in the absence of sexual intercourse. Given the small number of participants in this initial study, careful observation for potential irritation must also be included in larger studies of this and other vaginal formulations.

Administration, Intravaginal↗