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Biomedical subjects

J Smitz

Publications and source records attributed to J Smitz.

At least 73 records · Page 4Linked to original sources

Effect of topical applications of budesonide and azelastine on nasal symptoms, eosinophil count and mediator release in atopic patients after nasal allergen challenge during the pollen season.

We studied the activity of a topical form of a corticosteroid (budesonide) and an antihistamine (azelastine) in the treatment of seasonal allergic rhinitis by including an assessment of mediator concentrations and the percentage of eosinophils in the nasal secretions before and after the treatment. Nasal allergen challenge (NAC) during the season was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction. The study compared in a randomized way (2 parallel groups) the effect of budesonide (Rhinocort Aqua) and azelastine (Allergodil nasal spray) in a group of 14 patients during the pollen season. The study showed that azelastine significantly reduced sneezing, total nasal resistance and increased nasal airflow even when significant increases in histamine, tryptase and leukotriene C4 (LTC4) concentrations in nasal secretions were evidenced immediately after NAC. Budesonide showed a strong (p<0.05) decrease in infiltration and activation of eosinophils, and on tryptase and LTC4 release after NAC. These effects (not for LTC4) lasted at least for 1 week after therapy. Azelastine is a powerful topical antihistamine, while budesonide appears to be a potent long-acting anti-inflammatory agent.

Adolescent↗

Normal oxygen atmosphere is essential for the solitary long-term culture of early preantral mouse follicles.

This study compares the effects of reduced (5%) or normal (5% CO2 in air; 20% O2) oxygen tension on the in vitro maturation of early preantral ovarian follicles isolated from 14-day-old (C57BI/6J x CBAca) F1 mice. Intact follicles (100-130 microns) are singly cultured in 20 microliters droplets alpha-MEM enriched with FCS and rFSH under mineral oil at 37 degrees C and 100% humidity. In this culture system the follicles are allowed to attach to the bottom of the petri dishes. Follicle in vitro growth, hormone secretory capacity, and in vitro ovulation were studied under the two oxygen tensions. Spontaneous oocyte release from the follicle during a 16-day culture period was observed significantly more under 5% oxygen. Antral-like cavity formation was not observed under 5% O2. The follicles in the 5% O2 cultures reaching day 16 were stripped of their granulosa cell layers, and 83% of the retrieved oocytes had already undergone spontaneous germinal-vesicle breakdown (GVBD). Under 20% O2, the GV stage was maintained until day 16 in 77% of the oocytes. Under 5% O2, intact follicle survival up to day 12 was significantly reduced as compared to the 5% CO2 in air conditioning. The hCG stimulus on day 12 induced mucification in a significantly larger proportion of follicles cultured under 20% O2 (79% vs. 47%). Germinal-vesicle breakdown (20% O2:95, 5%, O2:42%) and first polar body extrusion (20% O2:40%, 5% O2:15%) were significantly more prevalent under normal oxygen tension. A reduced secretory capacity of E2 and inhibin was demonstrated for follicles cultured under 5% O2. The histological study of serially sectioned follicles showed increased areas of centrally located granulosa cell necrosis and pyknosis in the cumulus cells. Gassing follicle cultures using 5% CO2 in air provided appropriate conditions for normal growth, enhanced whole-follicle survival, differentiation, and hormone production, and improved the yield of meiotic competent oocytes.

Animals↗

Premature luteinization in in vitro fertilization cycles using gonadotropin-releasing hormone agonist (GnRH-a) and recombinant follicle-stimulating hormone (FSH) and GnRH-a and urinary FSH.

OBJECTIVE: To determine if premature luteinization can occur in GnRH agonist (GnRH-a) and FSH (recombinant FSH and human urinary FSH) IVF cycles and whether premature luteinization affects IVF and clinical outcome. DESIGN: Retrospective evaluation of 171 IVF-ET cycles. The cycles were divided into two groups according to the P level on the day of hCG: group I (serum P </= 0.9 ng/mL [conversion factor to SI unit, 3.180]) and group II (serum P >/= 1.1 ng/mL). MAIN OUTCOME MEASURES: Comparison of cycles characteristics and of cumulative exposure of follicular serum E2, FSH, LH, and P as well as of IVF and clinical outcome were made between the study groups. RESULTS: Twenty-three of the 171 cycles (13.4%) demonstrated premature luteinization. The age of the patients, the E2, and LH exposure were similar between the groups. The number of the ampules of gonadotropins (recombinant FSH and urinary FSH) used and the area under FSH and P curve were higher in cycles with premature luteinization. The area under the FSH curve correlated with the area under the P curve. Similar IVF and clinical outcomes were observed in cycles with and without premature luteinization. CONCLUSION: The greater FSH exposure and its correlation with the P exposure suggest that one of the possible factors inducing premature luteinization is the increased FSH-induced LH receptivity in granulosa cells. No adverse effects of premature luteinization on the IVF and clinical outcome were observed.

Adult↗

Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG.

This study is a long-term evaluation of the total pregnancy potential of cohorts of fresh and cryopreserved sibling embryos from in-vitro fertilization (IVF) cycles stimulated with either the gonadotrophin-releasing hormone analogue buserelin (BUS) (long protocol) or clomiphene citrate (CC) both in combination with human menopausal gonadotrophin (HMG). Therefore a retrospective analysis was performed on patients who entered the IVF programme between January 1986 and July 1987 and who had triple embryo transfer in the collection cycle. Significantly more fertilized oocytes developed to good-quality embryos in the CC-HMG group (86.1%) than in the BUS-HMG group (80.8%). Transfer of the three morphologically best-looking embryos was performed in day 2 post-insemination in 106 CC-HMG and 80 BUS-HMG cycles. Supernumerary embryos were cultured for a further 24 h and multicellular embryos with up to 20% of fragments were frozen slowly with 1.5 M dimethylsulphoxide on day 3 post-insemination (162 embryos in CC-HMG cycles, 102 embryos in BUS- HMG cycles). Outcome was measured by embryo survival rate, embryo implantation rate and delivery rate in fresh and frozen embryo transfers. Delivery rates were 31.3 and 21.7% per fresh embryo transfer in BUS-HMG and CC- HMG cycles respectively. Fresh embryo implantation rates were significantly higher in collection cycles stimulated with BUS-HMG (17.9%) than in cycles stimulated with CC-HMG (11.3%). Implantation rates were significantly enhanced in embryos transferred in excess of one in cycles leading to pregnancy, perhaps indicative of higher embryo quality in BUS-HMG cycles. Almost all cryopreserved embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated. Overall morphological survival rates of frozen-thawed embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated Overall morphological survival rates of frozen-thawed embryos were similar for 140 embryos from CC-HMG cycles (50%) and 100 embryos from BUS-HMG cycles (46%). The percentage of fully intact embryos was, however, significantly lower in the BUS-HMG group (19%) than in the CC-HMG group (39.5%). Delivery rates were significantly lower following 30 transfers of frozen-thawed embryos from BUS-HMG-stimulated cycles (3.3%) than following 42 transfers of frozen-thawed embryos from CC-HMG cycles (19.1%). Embryo implantation rates were lower for frozen-thawed embryos from BUS-HMG cycles (2.3%) than from CC-HMG cycles (12.7%). Here we demonstrate that ovarian stimulation with the long protocol BUS-HMG instead of the CC-HMG protocol led to higher embryo implantation rates in collection cycles but to lower intact embryo survival rates and to lower embryo implantation rates for frozen sibling embryos. Despite the lower implantation rates with frozen embryos originating from the BUS-HMG protocol, there was no significant difference between total delivery rate per transfer from cycles stimulated with CC-HMG (30.2%) compared with BUS-HMG (33.8%).

Adult↗

Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix).

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.

Adult↗

A morphological and functional study of the effect of slow freezing followed by complete in-vitro maturation of primary mouse ovarian follicles.

Mechanically isolated intact early preantral follicles (100-130 microns diameter) from 14 day old mice were cryopreserved by a slow freezing protocol with dimethyl sulphoxide and then matured in vitro for 12 days after rapid thawing. Minor freeze damage observed after 1 day of in-vitro culture included ablation of the theca cell layer and granulosa cell dehydration, resulting in disruption of intercellular contacts with the oocyte and between granulosa cells. Of the follicles, 24% were irreversibly damaged and had a collapsed oocyte. The remaining majority of the follicles had an intact oocyte as evaluated by ultrastructural analysis. Follicles with an intact oocyte were cultured in vitro and, after an initial retarded development, the final number of fully grown oocytes ovulated in vitro was not different from that of unfrozen controls. Cryopreserved early preantral follicles matured in vitro responded to stimulus with human chorionic gonadotrophin in a similar way to controls, with mucification of the oocyte-cumulus complex, germinal vesicle breakdown and extrusion of the first polar body of the oocyte. These cryopreserved, in-vitro matured oocytes had the potential to fertilize and develop to hatched blastocysts.

Animals↗

In-vitro maturation, fertilization and embryo development of immature oocytes from early preantral follicles from prepuberal mice in a simplified culture system.

A simplified culture system was developed for the in-vitro maturation of early preantral mouse ovarian follicles. The follicles were cultured singly in 20 microliters droplets under oil in medium supplemented with recombinant follicle stimulating hormone (r-FSH) at 37 degrees C and 5% CO2 in air. The follicles grew and became attached to the bottom of the dish, progressively lost their spherical structure by outgrowth of the granulosa cells through the basal membrane and developed follicles with antral-like cavities. The normal three-dimensional follicular structure was lost but all components, i.e. theca, granulosa and oocyte, remained functional, as was proven by the oestradiol, inhibin and progesterone secretion patterns. Follicle survival exceeded 80% and histological analysis proved the absence of atresia and cell death in granulosa cells up to day 16. Oocytes of 55 (+/-4) microns diameter on the day of isolation reached 74 (+/-3) microns by day 16 of culture. The optimal moment for inducing the final meiotic maturation with human chorionic gonadotrophin was investigated: the highest absolute numbers of metaphase II oocytes were obtained on days 12 and 14 (39 and 41%). The fertilizing potential of the in-vitro matured oocytes was comparable to in-vivo matured controls. A 50% hatched-blastocyst development rate was observed.

Animals↗

Female age predicts embryonic implantation after ICSI: a case-controlled study.

From 1 October 1991 until 31 December 1993, 1270 cycles for intracytoplasmic sperm injection were performed. Of these, 71 (5.6%) were carried out in women >/=40 years of age. The semen characteristics in couples >/=40 years of age or <40 years were similar. The mean male age for the older group of women was 47.1 years (range 34-67) versus 35 years (25-71) for the younger group of women (P < 0.001). The mean female age was 41.9 years (range 40-47) and 31.8 years (range 23-39). The numbers of cumulus-oocyte complexes and metaphase-II oocytes were significantly lower in women >/=40 years of age (P < 0.001). The mean numbers of replaced embryos were respectively 2.3 (133/59) in women >/=40 years of age and 2.5 (160/63) in women <40 years of age. The delivery rate per retrieval and per transfer was significantly lower in women >/=40 years of age (P < 0.05). The delivery rates per retrieval and per transfer were respectively 7% (5/71) and 8.5% (5/59) in the older group of women versus 22.5% (16/71) and 25.4% (16/63) in the younger group. Female age is the predictive factor for embryonic implantation.

Adult↗

Subtle progesterone rise after the administration of the gonadotrophin-releasing hormone antagonist cetrorelix in intracytoplasmic sperm injection cycles.

In the present study, subtle serum progesterone rise (>= 1.1 ng/ml) during the late follicular phase is reported, for the first time to our knowledge, in patients using a potent gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in combination with human menopausal gonadotrophin (HMG) for ovarian stimulation prior to intracytoplasmic sperm injection (ICSI). In five out of 24 patients (20%) serum progesterone levels were >/= 1.1 ng/ml. The cycle characteristics of the patients were similar in both groups. No premature endogenous luteinizing hormone (LH) surge occurred and the serum LH concentrations were constantly low during the follicular phase. The 17-beta oestradiol and follicle stimulating hormone (FSH) exposure were higher in cycles with premature luteinization. The greater oestradiol and FSH exposure confirm that one of the possible factors inducing subtle serum progesterone rise is the increased oestradiol and FSH-induced LH receptivity in granulosa cells.

Adult↗

Pregnancy and birth in an in-vitro fertilization cycle after controlled ovarian stimulation in a woman with a history of allergic reaction to human menopausal gonadotrophin.

We report a case of allergic reaction to i.m. injections of urinary human menopausal gonadotrophin (HMG) and a successful management of the problem by using recombinant follicle stimulating hormone (rFSH) administered i.m. The patient underwent two zygote intra-Fallopian transfer (ZIFT) cycles, in which ovarian stimulation was carried out by a combination of gonadotrophin-releasing hormone agonist (GnRHa) and HMG. A twin pregnancy was achieved after the first cycle. The patient delivered two premature boys at 28 weeks one of whom died after 25 days from severe respiratory distress. During the second ZIFT cycle the patient developed an allergic reaction with redness and swelling in many parts of her body 30 min after every HMG injection. Despite the allergic reaction, the cycle was completed with a second ZIFT. No pregnancy was achieved in this cycle. The patient came back to our centre for a third attempt during which ovarian stimulation was accomplished with a combination of GnRHa and rFSH. Adverse reaction as well as general discomfort were not reported by the patient during ovarian stimulation with rFSH. A successful singleton pregnancy was achieved after intrauterine embryo transfer with the birth of a healthy girl after 38 weeks. If any allergic reaction is present after injection of HMG it is advisable to stimulate a subsequent cycle with rFSH.

Adult↗

Concentrations of myeloperoxidase in nasal secretions of atopic patients after nasal allergen challenge and during natural allergen exposure.

A quantitative determination of myeloperoxidase (MPO) concentration was performed in the nasal secretions of atopic patients (challenged group, n = 17) after nasal allergen challenge outside the pollen season, and of patients with ongoing seasonal (seasonal group, n = 40) and with perennial (perennial group, n = 30) allergic rhinitis. The concentrations of MPO obtained from 10 nonallergic healthy volunteers (control group) were used as a normal control. Results showed that there was no statistical difference between the normal controls (median: 2.0 micrograms/g) and the atopic patients (median: 1.7 micrograms/g) outside the pollen season. After nasal allergen challenge (challenged group), there was no significant difference of MPO at 5 min (median: 1.0 microgram/G), 8 h (median: 1.7 micrograms/g), and 24 h (median: 3.1 micrograms/g) after challenge as compared to the baseline values. Also, there was no significant difference between patients with ongoing seasonal (median: 1.3 micrograms/g) or perennial (median: 1.8 micrograms/g) rhinitis, and atopic patients outside the pollen season. In conclusion, this study showed that MPO is not locally elaborated in measurable quantities in nasal secretions after nasal allergen challenge and during natural allergen exposure. Further studies will be needed to elucidate the role of neutrophils in the pathophysiological processes of allergic rhinitis.

Adolescent↗

Four radioisotopic immunoassays of free thyroxine compared.

The analytical and clinical performance of three radioisotopic methods for the measurement of free thyroxine-Gamma Coat (125I) Free T4, RIA-gnost FT4 and Amerlex-MAB* FT4-were assessed in comparison with the Scalvo two-step chromatographic method. The analytical evaluation indicated excellent performance of Amerlex-MAB FT4. For the other methods, precision and sensitivity were comparable and acceptable for routine use. Only Gamma Coat FT4 showed a significant positive intra-assay drift. None of the methods showed a significant correlation with thyroxine-binding globulin. Amerlex-MAB FT4 results were weakly positively correlated with albumin. Sclavo, RIA-gnost and particularly GammaCoat FT4 results were affected by the presence of increased concentrations of free fatty acids. All methods classified hyperthyroid patients correctly. Slight overlaps existed between the hypothyroid and euthyroid populations. Significant decreases in free thyroxine (FT4) during the third trimester of pregnancy were detected by all assays. In patients with chronic renal failure, serum FT4 was within reference limits more often when measured by Sclavo or Amerlex-MAB methods than by RIA-gnost or GammaCoat techniques. In conclusion, all assays performed well from both technical and diagnostic points of view.

Female↗

Effect of H1 and H2 antagonists on nasal symptoms and mediator release in atopic patients after nasal allergen challenge during the pollen season.

During the pollen season, quantitative determination of the chemical mediators and eosinophil count was performed in 16 patients with hay fever after nasal allergen challenge (NAC). The aim of this study was objectively to assess the effect of H1 and of a combination of H1 and H2 antagonists on nasal symptoms, mediator release, and eosinophil count during an allergic reaction. NAC was performed at baseline (V1), 2 weeks after treatment with cetirizine 10 mg/day (V2), and after a combined therapy with cetirizine 10 mg and cimetidine 800 mg a day during the following week (V3). Results showed a significant (p < 0.05 or p < 0.01) relief of nasal symptoms such as: itching, sneezing, rhinorrhea and congestion, and of objective parameter such as: reduction of the number of sneezes after NAC at V2 and V3. Neither H1 antagonist nor a combination of H1 and H2 antagonists showed any effect on eosinophilia and ECP concentration caused by natural allergen exposure, nor on histamine and tryptase release immediately after NAC. When a combination of H1 and H2 antagonists was administered significant reduction of the nasal airway resistance and increase of the nasal air flow were demonstrated.

Adult↗

Inflammatory cells and mediator concentrations in nasal secretions of patients with cystic fibrosis.

In this study, cytological examination of nasal secretions of 17 patients with cystic fibrosis (CF) was combined with quantitative determination of common inflammatory mediators. Results showed a normal cytogram in these patients. However, obvious mucosal inflammation is evidenced by significantly higher concentrations of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP). The activation of other common inflammatory cells such as mast cells (or basophils) and neutrophils could not be demonstrated since their mediators (histamine, tryptase and myeloperoxidase) are not raised. Increased concentrations of LTC4 and ECP indicate the active participation of eosinophils, and can contribute to the new concept of non-infectious inflammatory involvement of the nasal epithelium of patients with CF.

Adolescent↗

The activity of recent anti-allergic drugs in the treatment of seasonal allergic rhinitis.

Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy.

Adult↗

Results of microsurgical epididymal sperm aspiration (MESA) ans testicular sperm extraction (TESE) in azoospermic men using intracytoplasmic sperm injection (ICSI).

The rationale and results of using epididymal and testicular spermatozoa with intracytoplasmic sperm injection (ICSI) for zoospermic patients are reviewed. A total of 128 consecutive ICSI/MESA cycles and a total of 120 consecutive ICSI/TESE cycles were performed up to December 1994. The two-pronuclei fertilization rate per intact oocyte (observed after the injection) was 58% and 60%, respectively, when epididymal and testicular spermatozoa were used. The embryo transfer rate was similar for the two procedures (91% after ICSI/MESA and 90% after ICSI/TESE). Fifty women became pregnant (positive HCG) when epididymal spermatozoa were used (39% per cycle and 40% per embryo transfer). These results are comparable to those obtained when ejaculated spermatozoa are used.

Cell Separation↗

An early effect of acute plasma volume expansion in humans on serum erythropoietin concentration.

The effect of acute plasma volume change in humans on serum erythropoietin [EPO]s, plasma active renin [REN] and plasma aldosterone [ALDO] concentrations was examined. Plasma volume (PV) expansion was induced by intravenous infusion of 150 ml (30g) of plasma albumin and 500 ml of physiological saline. The [EPO]s decreased by 14.3% (corrected values for PV expansion) and remained decreased for 5 h. The [REN] was decreased by more than 25% during the day of the experiment and [ALDO] by more than 60%. Only a weak positive correlation was found between [EPO]s and [REN] (r = 0.35; P < 0.05) but a lack of correlation between changes in PV and [EPO]s as well as between [EPO]s and [ALDO] was seen. We postulated that in healthy men an acute PV expansion by 10% to 17.5% would not appear to promote stimulation of EPO synthesis for at least 11 h. Since a weak positive correlation was observed between [EPO]s and [REN] and a lack of correlation between [EPO]s and [ALDO], it would seem that there is no direct link between [REN] and [ALDO] and erythropoietin synthesis in healthy subjects.

Adult↗