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Biomedical subjects

S Campo

Publications and source records attributed to S Campo.

At least 19 recordsLinked to original sources
PubMed2000

Binding of bovine papillomavirus type 4 E8 to ductin (16K proteolipid), down-regulation of gap junction intercellular communication and full cell transformation are independent events.

The E8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide that contributes to primary cell transformation by conferring to cells the ability to form foci and to grow in low serum and in suspension. Wild-type E8 binds in vitro to ductin, a component of gap junctions, and this binding is accompanied by a loss of gap junction intercellular communication in transformed bovine fibroblasts. However, through the analysis of a panel of E8 mutants, we show here that binding of E8 to ductin is not sufficient for down-regulation of gap junction communication and that there is no absolute correlation between down-regulation of gap junction communication and the transformed phenotype.

Animals↗
PubMed1999

Sexual dimorphism in circulating monomeric and dimeric inhibins in normal boys and girls from birth to puberty.

BACKGROUND AND OBJECTIVE: Inhibins are peptides, mainly of gonadal origin, that suppress FSH production. Dimeric forms of inhibin (A and B) have been proposed as peripheral markers of Sertoli and granulosa cell function. The aim of this study was to establish the relationship between circulating dimeric and monomeric inhibins, and gonadotrophins and sex steroids, in normal boys and girls from birth to puberty. SUBJECTS: One hundred and forty-six normal children (females: 57; males: 89) were studied. MEASUREMENTS: Serum LH and FSH were measured by an immunofluorometric assay. Serum oestradiol and testosterone were measured by radioimmunoassay. Serum inhibin A and B, and Pro-alphaC, were measured by specific two-site enzyme-linked immunosorbent assays. RESULTS: In boys from birth to 6 months of age, the mean serum inhibin B concentration was as high (477 +/- 53.7 ng/l) as that found at puberty (400 +/- 70.2 ng/l). After the first year, inhibin B gradually decreased to reach its lowest concentration (153 +/- 23.6 ng/l) at age 4-6 years. At approximately age 10, it rose progressively to reach pubertal concentrations. Pro-alphaC showed a similar pattern but at lower concentrations. Inhibin A was not detected at any age. In girls from birth to 6 months, inhibin B levels (83.0 +/- 18.3 ng/l) were approximately 50% lower than those found at puberty (181 +/- 25.7 ng/l). After 6 months of age, these levels dropped (17.5 +/- 1.6 ng/l) and remained low until the prepubertal years. Thereafter, they increased to pubertal concentrations. The serum inhibin A concentration after birth (29.9 +/- 8.7 ng/l) was similar to that found at puberty (18.3 +/- 5.7 ng/l); after 6 months, it fell to undetectable levels until the prepubertal years. CONCLUSION: The sex difference in serum levels of gonadotrophins is associated with sex differences in the levels and proportions of circulating dimeric and monomeric inhibins.

Adolescent↗
PubMed1999

Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophin-releasing hormone analogues.

The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone (GnRH) analogue treatment prior to laparoscopic myomectomy. From June 1993 through December 1996, 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart, Rome. According to a computer-generated sequence, 30 patients were submitted to three cycles of GnRH analogue treatment prior to surgery, whereas no preoperative treatment was prescribed to the other 30 patients. Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically. The patients' mean age, the number of myomas per patient, the mean diameter of the myomas, parity and estimated blood loss were similar in both groups. The operative time was significantly longer in the group of patients submitted to GnRH analogue treatment than that of the group of patients not submitted to any preoperative medical therapy (157.5 +/- 74.71 versus 112.33 +/- 54.71 min; P = 0.01). No intra-operative complications occurred. In no case was blood transfusion necessary. Two patients developed post-operative fever (temperature > 38 degrees C.). The mean length of hospital stay was 2.39 days and was similar in both groups. Thirteen spontaneous pregnancies occurred among 24 infertile patients (54.1%). The pregnancy rate for these patients was similar in both groups. The viable term delivery rate was 45.8%. The authors conclude that laparoscopic myomectomy is a feasible and safe procedure. The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy. The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy.

Adult↗
PubMed1999

Androgen regulation of immunological and biological activities of pituitary follicle-stimulating hormone isoforms in male rats.

Follicle-stimulating hormone (FSH) is involved in the regulation and maintenance of gametogenesis. It exists in multiple molecular forms with different oligosaccharide structures which in turn are influenced by the hormonal milieu. Previous studies from our laboratory demonstrated that antiandrogen administration to immature male rats altered the biological activity and the distribution profile of pituitary FSH isoforms. The aim of this study was to examine possible modifications in pituitary FSH polymorphism throughout sexual development (10-, 32- and 75-day-old rats). In addition, the effect of androgen deprivation by castration (32-day-old rats) and its replacement with a nonaromatizable androgen - dihydrotestosterone - on pituitary FSH polymorphism was determined. Concanavalin A affinity chromatography was used to isolate groups of FSH isoforms according to their carbohydrate inner structure. Radioimmunoassay and Sertoli cell bioassay were used to evaluate FSH immuno- and bioactivities. Androgen rise in serum was accompanied by a marked increase in pituitary bio- and immuno-FSH content in 32- and 75-day-old rats. However, FSH pituitary content did not vary despite the significant increment observed in serum FSH levels after castration and decrease to control levels after androgen replacement. The distribution profile of immuno- and bioactive FSH changed throughout sexual maturation. The proportion of pituitary FSH isoforms bearing complex oligosaccharide structures (triantennary, bisecting, complete and truncated biantennary) increased with age, with a concomitant decrease in the proportion of isoforms bearing incomplete carbohydrate chains. The distribution profile observed in castrated 32-day-old rats was similar to that determined in 10-day-old animals. Androgen replacement restored the distribution profile to normal. These results suggest that androgens regulate the incorporation of sugar residues to the carbohydrate chains of pituitary FSH favoring the biosynthesis of complex-type oligosaccharide structures.

Animals↗
PubMed1999

Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells.

In the present study, we have examined the role of hormones and growth factors in regulating dimeric inhibin production in immature rat granulosa cells. Purified granulosa cells from estrogen-primed immature rats were cultured under defined conditions. Inhibins A and B in the culture media were measured using a two-site enzyme-linked immunosorbent assay specific for each dimer. Under basal conditions, granulosa cells produced 14-fold more inhibin A than inhibin B (inhibin A, 2.0; inhibin B, 0.14 ng/ml, measured against human standards; average A/B apparent ratio, 14). Addition of increasing doses of FSH elicited dose-dependent increases in both inhibins, the effects being more pronounced on inhibin A than on inhibin B (9.4- and 4.1-fold increases, respectively; average A/B ratio, 34). Estradiol, when added alone, stimulated inhibin A production 3- to 6-fold, whereas minor changes were observed in inhibin B production. Insulin-like growth factor-I produced a similar stimulation of both inhibins (3-fold stimulation over control). This growth factor, however, induced a marked dissociation in the sensitivity of inhibins A and B to FSH stimulation, with maximal stimulation of inhibin B observed at comparatively lower concentrations of the gonadotropin. Transforming growth factor-beta (TGF-beta, 5 ng/ml) had a more marked stimulatory effect on inhibin B than on inhibin A production (7- to 14-fold vs. 2- to 5-fold for inhibin B and A, respectively). A more pronounced differential stimulation of inhibin B was also exerted by another member of the TGF-beta superfamily, activin A (A/B ratio, 0.66). This preferential stimulation of inhibin B by TGF-beta and activin A was amplified in the presence of FSH. Coculture of rat granulosa cells with freshly isolated bovine oocytes was also associated with a marked stimulation of inhibin B production (100-fold increase) and a comparatively lower stimulation of inhibin A (10-fold increase; A/B ratio, 1). The discrepancy between the proportion of inhibin dimers in serum (A/B ratio, 0.13) and those produced by untreated granulosa cells may suggest that intraovarian factors, such as TGF-beta, activin A, or oocyte-derived factor(s), are responsible for the shift of the ratio toward the predominance of inhibin B.

Animals↗
PubMed1999

Plasma levels of E-selectin in normolipemic and hyperlipemic arteriopathic patients.

BACKGROUND: The authors studied the plasmatic levels of E-selectin in a group of normolipemic and hyperlipemic arteriopathic patients. METHODS: The series consisted of 73 subjects (53 male, 20 female, age 54 +/- 9) suffering from occlusive peripheral arteriopathy; 21 subjects with total cholesterol (TC) below 200 mg/dl were considered as normolipemics (group A), 24 subjects with TC between 200 and 240 mg/dl, mild hypercholesterolemics (group B), 18 with TC above 240 mg/dl, severe hypercholesterolemics (group C); 10 subjects had high triglyceride values (above 200 mg/dl), (group D); 12 normal controls were also considered. For each subject the determination of the E-selectin E-plasma levels was performed with an immunoenzymatic method (kit ELISA Amersham). RESULTS: In group A a value of E-s (4.03 +/- 0.37 ng/ml) statistically lower (p < 0.05) compared to normal controls (5.71 +/- 0.61 ng/ml) was found; in group B the E-s value (3.81 +/- 0.31 ng/ml) was slightly lower than that of group A; in group C the value of E-s was 3.53 +/- 0.23 ng/ml, statistically lower compared normal controls (p < 0.01) and to group A (p < 0.05); in group D the E-s value (3.24 +/- 0.23 ng/ml) was sharply reduced compared to controls (p < 0.01) and to groups A-B-C (p < 0.05). CONCLUSIONS: The reduction or E-selectin, was proportional to the magnitude of total cholesterol and triglycerides; the chronicity of the vasculopathy and the dyslipidemia may be responsible for an impaired biosynthetic endothelial function.

Arterial Occlusive Diseases↗
PubMed1998

Beneficial effect of raxofelast, an hydrophilic vitamin E analogue, in the rat heart after ischemia and reperfusion injury.

Several studies report that among the antioxidant agents used to reduce injury after myocardial ischemia/reperfusion, analogues of vitamin E (VE) seem to have a significant efficacy. Raxofelast is a potent antioxidant agent under investigation, structurally related to VE, having an excellent bioavailability and favourable physicochemical properties. We assessed raxofelast in a rat model of myocardial damage induced by 1 h of left coronary artery occlusion followed by 6 h of reperfusion. Myocardial ischemia/reperfusion produced: wide tissue necrosis (50.3+/-10.3%); membrane peroxidation, evaluated by assessing cardiac malondialdehyde (MAL) (87.8+/-15.8 nmol/g tissuev 9.53+/-2.4 nmol/g tissue) and plasma conjugated dienes (CD) (8.73+/-1.86 DeltaABS/mlv 1.61+/-0.45 DeltaABS/ml); endogenous antioxidant wasting [cardiac VE=23.5+/-10.2 nmol/g tissuev 61.4+/-13.4 nmol/g tissue, cardiac reduced glutatione (GSH)=2.15+/-1.23 micromol/g proteinv 7.34+/-0.92 micromol/g protein and cardiac superoxide dismutase (SOD)=8.9+/-4.1 U/mg proteinv 17. 5+/-4.2 U/mg protein]; depressed mean arterial blood pressure (MAP) (61.4+/-5.8 mmHgv 85.3+/-6.2 mmHg); heart rate (HR) (275+/-35 beats/minv 368+/-34 beats/min) and left-ventricular derivative developed force (LV dP/dtmax) (1050+/-187 mmHg/sv 2520+/-194 mmHg/s); and cardiac neutrophil accumulation, evaluated by assessing cardiac myeloperoxidase (MPO) (9.23+/-2.1 U/g tissuev 0.92+/-0.12 U/g tissue). Administration of raxofelast (25, 50 and 100 mg/kg i.p. 5 min after occlusion) limited myocardial necrosis (22.3+/-14.8%P<0. 005, following the highest dose), reduced lipid peroxidation (MAL=43. 5+/-14.7 nmol/g tissueP<0.001 and CD=4.01+/-2.21 DeltaABS/mlP<0.001, following the highest dose), restored the endogenous antioxidants VE (52.8+/-14.2 nmol/g tissueP<0.001, following the highest dose), SOD (14.2+/-2.7 U/mg proteinP<0.001, following the highest dose) and GSH (4.92+/-1.33 micromol/g proteinP<0.005, following the highest dose), improved hemodynamic parameters (MAP=68.1+/-5.3 mmHgP<0.05, HR=317+/-27 beats/minP<0.05, LV dP/dtmax=1427+/-143 mmHg/sP<0.05, following the highest dose) and reduced myocardial neutrophil infiltration (MPO=5.1+/-1.5 U/g tissueP<0.001, following the highest dose). These data suggest that raxofelast could be considered a useful drug to reduce myocardial infarction.

Alkenes↗
PubMed1998

Laparoscopic gonadectomy in two patients with gonadal dysgenesis.

Individuals with androgen insensitivity syndrome have a high risk (20-30%) of developing malignancy in their gonads. Accordingly, bilateral gonadectomy is recommended. In a 17-year-old woman with Swyer syndrome gonads were located as streaks above the pelvic brim. In a 13-year-old with Morris syndrome they were located within the inguinal canals. Bilateral laparoscopic gonadectomy was performed under general anesthesia in both patients without complications. We suggest that in phenotypic females with 46,XY karyotype, the procedure may be performed safely, even with gonads located in inguinal canals.

Adolescent↗
PubMed1998

Laparoscopic conservative excision of ovarian dermoid cysts with and without an endobag.

STUDY OBJECTIVE: To compare outcomes of conservative laparoscopic treatment of dermoid cysts removed from the abdominal cavity without (group A) and with an endobag (group B). DESIGN: Prospective, randomized, 4-year (June 1992-June 1996) study (Canadian Task Force classification I). SETTING: Department of Obstetrics and Gynecology of the Catholic University of the Sacred Heart in Rome. PATIENTS: Fifty-five premenopausal women with dermoid cysts. Intervention. Patients were randomly assigned to removal of dermoid cysts from the abdominal cavity with or without an endobag through a 10- to 12-mm cannula sleeve. MEASUREMENTS AND MAIN RESULTS: We assessed surgical time, spillage, complications, length of hospitalization, recurrences, and pregnancies. In the 55 women, 58 dermoid cysts (mean diameter 5.6 +/- 2.03 cm) were enucleated and removed at operative laparoscopy through a 10- to 12-mm cannula sleeve without intraoperative or postoperative complications. Mean operating time was 73 minutes. When cysts were removed with an endobag, operating time was significantly reduced over removal without the endobag (63 vs 81 min, p <0.05). Obvious spillage of endocystic contents occurred in 13 (43.3%) patients in group A but in only 1 patient in group B because the bag ruptured (p <0.05). No signs or symptoms of peritonitis were observed in women with evident cystic spillage or in those in group A in whom spillage was possible. Average postoperative hospital stay was 1.7 days and did not differ between groups. Among 20 infertile women, 9 (45%) experienced spontaneous pregnancy within a year, with no differences between groups. Echographic follow-up did not reveal cyst recurrence. CONCLUSIONS: Laparoscopic conservative cystectomy of dermoid cysts in premenopausal women is safe and effective and appears to be a valuable alternative to laparotomy. Removing cysts in an endobag significantly reduced both operating time and spillage. However, controlled intraperitoneal spillage of cyst contents does not increase postoperative morbidity as long as the peritoneal cavity is thoroughly washed.

Adolescent↗
PubMed1998

Characterization of serum SHBG isoforms in prepubertal and pubertal girls.

OBJECTIVE: SHBG is a circulating glycoprotein that binds dihydrotestosterone, testosterone and oestradiol with high affinity and low capacity. In girls, serum concentrations of SHBG gradually decrease with age due to a true fall in concentration and not to a change in the binding characteristics. The aim of our study was to determine the pattern of serum SHBG isoforms in normal girls in early childhood (ECh), late childhood (LCh) and puberty (P). SUBJECTS: Fifteen normal girls were studied. They were divided into three groups according to their age: ECh: 3.7 +/- 0.9 years (mean +/- SD, n = 5); LCh: 6.4 +/- 0.5 years (n = 5); and P: 13.4 +/- 1.5 years (n = 5). METHODS AND MEASUREMENTS: Preparative isoelectric focusing was used to isolate SHBG isoforms according to their isoelectric point (pI). Three groups of isoforms were isolated: SI: pI 5.2-5.4; SII: pI 5.4-5.6 and SIII: pI 5.6-5.8. Steroid levels in serum were determined by RIA. RESULTS: The relative distribution of SHBG isoforms (% of the total SHBG recovered, mean +/- SD) in the three groups of girls studied was: ECh: SI: 25.8 +/- 9.9, SII: 53 +/- 10.5 and SIII: 21.2 +/- 1.6; LCh: SI: 8.8 +/- 3.1, SII: 58.8 +/- 12.2 and SIII: 31.8 +/- 8.6; P: SI: non-detectable; SII: 51.6 +/- 12.6 and SIII: 48.4 +/- 12.6. CONCLUSION: These results indicate that serum SHBG is more heterogeneous before puberty. A considerable proportion of acidic isoforms are present early in life; they decrease during the prepubertal period and disappear when sexual development is completed. After puberty the glycoprotein is more homogeneous and an important proportion of more basic isoforms is present. At puberty serum SHBG not only falls in concentration but also has an altered sialic acid content which modulates its circulating half-life.

Adolescent↗
PubMed1998

Ovulatory cycles, pregnancy outcome and complications after surgical treatment of polycystic ovary syndrome.

The purpose of this review is to survey the literature on the various laparoscopic surgical techniques for ovulation induction in polycystic ovary syndrome (PCOS) patients (multiple biopsies, electrocauterization, laser vaporization, ovarian resection), compared with traditional ovarian resection by laparotomy. Relevant studies were identified through a search of a computerized bibliographic database and cross-referencing of relevant medical journals. Data regarding 1803 anovulatory PCOS patients have been analyzed, 679 of them treated by classical ovarian resection after laparotomy, 720 by laparoscopic electrocauterization, 322 by laparoscopic laser vaporization, and 82 by laparoscopic multiple biopsies. The percentages of miscarriages, twin pregnancies, and ectopic pregnancies have been calculated analyzing 1076 pregnancies achieved spontaneously or after medical therapy after failure of various surgical attempts. The percentage of adhesions has been calculated among 343 patients submitted to second-look surgery. All of the surgical techniques proved equally effective, with an average ovulation rate of 78.8 percent, a cumulative pregnancy rate of 58.5 percent, a miscarriage rate of 15.9 percent, a twin pregnancy rate of 2.1 percent, and an ectopic pregnancy rate of 1.6 percent. Hormone variations after surgery consisted in a remarkable fall in serum androgen levels (androstenedione and testosterone), in an FSH increase, reduced biological activity and reduced amplitude of LH pulses, and an LH/FSH ratio trending toward normal levels. Moreover, after surgery, the ovaries showed higher responsiveness to drug-induced ovulation. Adhesions were less frequent after laparoscopic multiple biopsies, but they were observed in about 90 percent of patients after resection by laparotomy, in 30 percent of patients after laparoscopic electrocauterization, and in 50 percent after laparoscopic laser vaporization. In conclusion, at present laparoscopic methods for inducing ovulation can be performed in PCOS infertile patients if medical treatment fails to give the desired results. However, additional controlled trials are required to assess the long-term effects of these procedures.

Anovulation↗
PubMed1998

Spontaneous pregnancy after 13 years of amenorrhea in a patient with a voluminous ovarian dysgerminoma and submitted to left adnexectomy and radiotherapy.

The authors illustrate the case of a 17-year-old patient who was submitted to left adnexectomy in view of an ovarian dysgerminoma 24 cm in diameter and weighing 2,800 g. She was subsequently submitted to two cycles of radiotherapy. Following a period of amenorrhea lasting 13 years and characterized by high serum levels of gonadotropins, the patient had a spontaneous pregnancy and at 33 weeks of gestation delivered a live and vital fetus. Therefore the occurrence of post-radiotherapy amenorrhea, characterized by high serum gonadotropin levels, should not always be considered pathognomonic of precocious menopause. The possibility that radiotherapy causes only a temporary alteration in ovarian activity should also be taken into consideration.

Adolescent↗
PubMed1998

Efficacy assessment of highly purified follicle-stimulating hormone alone or in combination with human menopausal gonadotropin during pituitary suppression in patients undergoing GIFT for unexplained infertility.

The purpose of this study was to compare the efficacy of highly purified follicle-stimulating hormone (FSH-HP) alone versus the combination of FSH-HP + human menopausal gonadotropin (hMG) treatment during pituitary suppression with gonadotropin-releasing hormone (GnRH) analog on the clinical outcome and endocrine parameters in 120 randomized women undergoing gamete intra-Fallopian transfer (GIFT) for unexplained infertility. Our data did not show any significant difference between the two groups as regards dose of administered gonadotropins, duration of treatment, estradiol 17 beta 17 beta increase curves, number of follicles > 16 mm, number of recruited and transferred oocytes, and endometrial thickness. The percentages of clinical pregnancies (33.3% with FSH-HP and 31.6% with FSH-HP + hMG), of miscarriages and twin gestations were also similar in the two groups. It is concluded that, during GnRH analog suppression, FSH-HP treatment alone is effective in inducing normal follicular steroidogenesis and adequate oocyte maturation, but no detrimental effect of luteinizing hormone (LH) activity of hMG on the outcome of the outcome of ovarian stimulation was found.

Adult↗
PubMed1998

Protective effects of the new lazaroid "U-83836E" in splanchnic artery occlusion (SAO) shock.

We studied the effects of the new antioxidant drug U-83836E during splanchnic artery occlusion (SAO) shock in the rat. Serum tumor necrosis factor (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure (MAP), survival rate and the responsiveness to acetylcholine of aortic rings were investigated. SAO shock produced a marked increase in serum TNF-alpha (241.4 +/- 18.2 U/ml vs Not Detectable in basal), reduced MAP (51.4 +/- 4 mmHg vs 85.1 +/- 5 mmHg), survival time (80 +/- 10 min vs > 240 min), WBC count (2.8 +/- 0.4 x 10(3)/mm3 cells vs 11.7 +/- 0.9 x 10(3)/mm3 cells) and blunted the responsiveness to ACh of aortic rings (60 +/- 3% tension vs 23 +/- 4% tension). The analogue of vitamin E, U-84836E, administered at onset of reperfusion, lowered serum TNF-alpha (38.4 +/- 6.5 U/ml; p < 0.001), improved MAP (67.5 +/- 3.8 mmHg; p < 0.001), WBC count (8.9 +/- 0.6 x 10(3)/mm3; p < 0.001), and survival time (235 +/- 15 min; p < 0.001), and restored the responsiveness to ACh of aortic rings (32 +/- 3.7% tension; p < 0.001). These preliminary data suggest that this new compound could be a promising drug in shock therapy.

Acetylcholine↗
PubMed1998

[The ICSI (Intracytoplasmic Sperm Injection)].

ICSI (Intracytoplasmic Sperm Injection) is the latest known assisted reproduction technique (ART) and it already appears to be mature. In fact the analysis of the results presented by the researchers over the years has shown that the most specific indication for this ART is the sterility of the couple with serious male pathology, up to ejaculatory azoospermia where it is possible to perform MESA, PESA or TESE. Any kind of sterility could be solved with ICSI whose only limit presently known is the high technology and therefore high costs involved. The percentage of oocytes that undergo ICSI without being damaged varies from 87% to 94% and the percentage of fertilization varies from 33% to 71%. The transfer rate is 59-100%. The rate of pregnancies per couple ranges from 12% to 40% of the couples, from 11% to 41% for the transfers. Since abortions are similar to the values of the normal population (10-15%), ICSI is actually the assisted fertilization technique with the highest incidence of pregnancies and "take home babies". The percentage incidence of the two sexes, of the malformations and the typologies of malformations corresponds to those observed in the population with spontaneous pregnancies. Since there is no natural selection of the gametes in ICSI, one may be sure that when spermatozoa with any kind of pathology are injected, the pregnancy does not take place at all.

Cytoplasm↗
PubMed1997

Pre-S2 defective hepatitis B virus infection in patients with fulminant hepatitis.

Controversial data were recently published concerning the association of hepatitis B virus (HBV) variants with fulminant hepatitis (FH). In this study, we first analyzed the complete nucleotide sequences of HBV genomes isolated from serum samples from a surgeon and his mother, who was accidentally infected by the son; both died of FH. The infecting viruses were genetically almost identical in both patients; all the clones examined carried a double nucleotide mutation in the start codon of the pre-S2 region that prevented the synthesis of the corresponding protein. Analyses of different serum samples from the son revealed only wild-type precore sequences in a high viremic serum, whereas hepatitis B e antigen (HBeAg)-defective strains were prevalent when the viremia had decreased. Subsequently, we extended the analysis to the viral genomes isolated from 18 additional patients with acute HBV infection and different clinical behaviors: 3 of 5 patients with FH and without previous liver disease had pre-S2 start codon mutations preventing pre-S2 protein synthesis, whereas none of the 13 control cases had similar genomic rearrangements. Analysis of the precore region showed that viral populations normally producing HBeAg were the only or the prevalent viral strains in all of these cases. In summary, our results support the hypothesis that the pre-S2 protein is not essential for HBV infectivity. They also show that infection by pre-S2-defective virus is frequently associated with FH, indicating that this variant might play a pathogenetic role in cases of acute liver failure. Finally, they suggest that the emergence of HBeAg-defective viruses might be a late event in the course of FH, occurring when HBeAg-producing viruses have been mostly cleared.

Acute Disease↗
PubMed1997

Esophageal dysmotility and gastroesophageal reflux in intrinsic asthma.

This study was undertaken to determine the prevalence of esophageal motor abnormalities, the incidence of gastroesophageal reflux, and the coexistence of gastroesophageal reflux with esophageal dysmotility in patients with intrinsic asthma. Based on clinical criteria, 34 consecutive asthmatics, 15 patients with gastroesophageal reflux, and 10 subjects with upper gastrointestinal symptoms with normal results of esophageal manometry and 24-hr esophageal pH test (controls) were studied. Esophageal motor disorders were noted in 23 of 34 asthmatics, and in 10 of 15 patients with acid reflux but in none of the subjects of the control group. A positive result of the prolonged esophageal pH study (pH in the distal esophagus less than 4 for more than 4.2% of the recording time) was obtained in 14 of 17 patients with asthma (only 17 of the original patients were tested because the others did not give informed consence for this test) and in all patients with gastroesophageal reflux. None of the members of the control group had positive test results. The findings of this study show that: (1) it is possible to identify a group of subjects with nonallergic asthma presenting with esophageal dysmotility, (2) the 24-hr esophageal pH study must be properly done in such patients; (3) esophageal motor abnormalities are often associated with positive pH results; and (4) more reflux was observed while in a supine position (especially during the night) than that observed either in control or reflux patients. Based on these results, patients with intrinsic asthma with reflux can benefit from both acid suppressive and prokinetic drugs with notable clinical implications regarding standard treatment for asthma, and those with prevalent supine compared to upright reflux could even benefit from surgery.

Asthma↗