The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

The article "The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials", by V. Panetta, A. Bacchieri, S. Papetti, E. De Stefani, P. Navarra, published in Eur Rev Med Pharmacol Sci 2020; 24 (2): 963-973-DOI: 10.26355/eurrev_202001_20082-PMID: 32017005, has been retracted based on commentary received from a new set of reviewers.  The authors will be able to resubmit a new article addressing the reviewers' comments for the Journal's consideration. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20082.

Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

OBJECTIVE: A high-concentration of a multi-strain probiotic mixture, VSL#3® is widely used 'whenever it is useful to promote the balance of intestinal flora'. As a food supplement, VSL#3® has been so far scarcely investigated on the aspect of safety. To fill this gap, in this paper, we analyzed the adverse events (AEs) recorded during the conduct of three (3) double-blind, randomized, placebo-controlled trials carried out to explore the efficacy of VSL#3® in various clinical settings. Data from a large open-label observational trial were also considered. MATERIALS AND METHODS: All trials included in the analysis were carried out according to good clinical practice (GCP) rules. AEs were classified by System Organ Class (SOC), Preferred Term (PT) and frequency. Differences vs. placebo control were considered as statistically significant if the p-value was < 0.05. RESULTS: A total of 120 patients were analyzed, 70 patients being included in the randomized controlled trials. In this population, 45 patients had at least one AE, 20 (64.5%) in the placebo group and 25 (64.1%) in the VSL#3® group. 29 patients had at least one related AE, 14 (45.2%) and 15 (38.5%) in the two treatment groups, respectively. Only one AE was assessed as serious, i.e., Foetal malformation, which occurred in the placebo group and was considered unrelated. No significant difference was found between VSL#3® and placebo for any of the SOC considered, with the exception of Injury, poisoning and procedural complications, which was in favor of VSL#3®. CONCLUSIONS: Based on GCP-quality data from clinical trials, we conclude that VSL#3® is a safe and well-tolerated agent.

Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules.

BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood. METHODS: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration. CONCLUSIONS: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.

Flow-synchronized nasal intermittent positive pressure ventilation for infants <32 weeks' gestation with respiratory distress syndrome.

Aim. To evaluate whether synchronized-NIPPV (SNIPPV) used after the INSURE procedure can reduce mechanical ventilation (MV) need in preterm infants with RDS more effectively than NCPAP and to compare the clinical course and the incidence of short-term outcomes of infants managed with SNIPPV or NCPAP. Methods. Chart data of inborn infants <32 weeks undergoing INSURE approach in the period January 2009-December 2010 were reviewed. After INSURE, newborns born January -December 2009 received NCPAP, whereas those born January-December 2010 received SNIPPV. INSURE failure was defined as FiO(2) need >0.4, respiratory acidosis, or intractable apnoea that occurred within 72 hours of surfactant administration. Results. Eleven out of 31 (35.5%) infants in the NCPAP group and 2 out of 33 (6.1%) infants in the SNIPPV group failed the INSURE approach and underwent MV (P < 0.004). Fewer infants in the INSURE/SNIPPV group needed a second dose of surfactant, a high caffeine maintenance dose, and pharmacological treatment for PDA. Differences in O(2) dependency at 28 days and 36 weeks of postmenstrual age were at the limit of significance in favor of SNIPPV treated infants. Conclusions. SNIPPV use after INSURE technique in our NICU reduced MV need and favorably affected short-term morbidities of our premature infants.

Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis.

AIMS: Recent data in mouse and rat demyelination models indicate that administration of thyroid hormone (TH) has a positive effect on the demyelination/remyelination balance. As axonal pathology has been recognized as an early neuropathological event in multiple sclerosis, and remyelination is considered a pre-eminent neuroprotective strategy, in this study we investigated whether TH administration improves nerve impulse propagation and protects axons. METHODS: We followed up the somatosensory evoked potentials (SEPs) in triiodothyronine (T3)-treated and untreated experimental allergic encephalomyelitis (EAE) Dark-Agouti female rats during the electrical stimulation of the tail nerve. T3 treatment started on the 10th day post immunization (DPI) and a pulse administration was continued until the end of the study (33 DPI). SEPs were recorded at baseline (8 DPI) and the day after each hormone/ vehicle administration. RESULTS: T3 treatment was associated with better outcome of clinical and neurophysiological parameters. SEPs latencies of the two groups behaved differently, being briefer and closer to control values (=faster impulse propagation) in T3-treated animals. The effect was evident on 24 DPI. In the same groups of animals, we also investigated axonal proteins, showing that T3 administration normalizes neurofilament immunoreactivity in the fasciculus gracilis and tau hyperphosphorylation in the lumbar spinal cord of EAE animals. No sign of plasma hyperthyroidism was found; moreover, the dysregulation of TH nuclear receptor expression observed in the spinal cord of EAE animals was corrected by T3 treatment. CONCLUSIONS: T3 supplementation results in myelin sheath protection, nerve conduction preservation and axon protection in this animal model of multiple sclerosis.

Understanding the implications of the PAX9 gene in tooth development.

AIM: Tooth agenesis is characterised by the congenital absence of one or more teeth. The Pax9 gene has been associated with nonsyndromic forms. MATERIALS AND METHODS: To investigate the molecular mechanisms, we evaluated specific haplotypes frequency in exon 3 of the Pax9 gene in 26 patients and 21 controls, using an Italian population. RESULTS: Presence of His239His and the Ala240Pro were confirmed in exon 3 of the Pax9 gene. A frequency of 20.2€ of the T allele at position 717 and a C frequency of 33€ of Ala240Pro polymorphism, that reached 40.5€ in the control group, were observed. The 39 C/C-240 C/C or G/Chaplotype which we defined Pax9hapl a had a proportion of 61.9€ in control individuals. The frequency of Pax9hapl a tested in the patients was different from controls, being 81.3€ in normalcy and 18.8€ in oligodontia (p<0.05). CONCLUSION: Our observations suggest that Pax9hapl a may have a protective effect against sporadic oligodontia.

Accuracy of three age determination X-ray methods on the left hand-wrist: a systematic review and meta-analysis.

Age estimation of living individuals often represents a forensic challenge with important legal and social implications. In an effort to better understand the accuracy of the methods of Greulich and Pyle (GP), Tanner-Whitehouse (TW) and Fels, a systematic review and a meta-analysis of articles published from 1956 to 20 December 2009 in the Medline and Trip databases were conducted. We only selected articles on healthy people. The meta-analysis showed that GP is not as accurate a method as TW2 or TW3 for both Caucasian people and Mongoloids, even if it is the one most often used. However, due to the very wide age estimation range, in line with what has already been established by several authors, our systematic review and meta-analysis confirmed that age estimation in living individuals cannot be considered accurate when only X-ray methods on the left hand-wrist are used, but exhaustive combinations of various procedures (i.e. physical examination, dental and skeletal methods) must also be used, as proposed and already applied by the International Study Group on Forensic Age Estimation.

Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants.

In recent years, Staphylococcus aureus has become a common bowel colonizer in Swedish infants. We aimed to identify host factors that determine such colonization. Stool samples from 100 Italian and 100 Swedish infants were obtained on seven occasions during the first year of life and cultured quantitatively for S. aureus. In a subgroup of infants in each cohort, individual strains were identified by random amplified polymorphic DNA analysis. Colonization at each time-point was related to delivery mode, siblings in family and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish infants had S. aureus in their stools on at least one time-point (p 0.08) and 4% of Italian and 27% of Swedish infants were positive on at least six of the seven time-points investigated (p 0.0001). Most infants analysed regarding strain carriage harboured a single strain in their microbiota for several months. The S. aureus stool populations in colonized infants decreased from 10(7) to 10(4) colony-forming units/g between 1 week and 1 year of age in both cohorts. In multivariate analysis, the strongest predictor for S. aureus colonization was being born in Sweden (OR 3.4 at 1 week of age, p 0.002). Having (an) elder sibling(s) increased colonization at peak phase (OR 1.8 at 6 months, p 0.047). Antibiotic treatment was more prevalent among Italian infants and correlated negatively with S. aureus colonization at 6 months of age (OR 0.3, p 0.01). To conclude, S. aureus is a more common gut colonizer in Swedish than Italian infants, a fact that could not be attributed to feeding or delivery mode.

Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants.

Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson's Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities.

Lack of efficacy of topical furfuryl palmitate in pediatric atopic dermatitis: a randomized double-blind study.

INTRODUCTION: Atopic dermatitis is a common disease in children. It is usually treated with topical steroids and/or calcineurin inhibitors in association with emollients but topical antioxidants have been recently introduced as a therapeutic option for children. The aim of this study was to evaluate the efficacy and tolerability of furfuryl palmitate, a new antioxidant molecule, in a multicenter, randomized, double-blind, vehicle-controlled study. PATIENTS AND METHODS: Children with atopic dermatitis were randomized into 2 groups treated for 2 weeks. One group of children (n = 60) was treated with a basic emollient cream and the other (n = 57) was treated with the same cream enriched with furfuryl palmitate. RESULTS: In both groups, there was a significant reduction (P < .001) in atopic dermatitis-measured using the SCORAD index-after 14 days. The reduction in the per-protocol analysis was higher for the basic cream. Treatment success was defined as a reduction of 20% or more in the SCORAD index from baseline to day 14. Patients who used treatment not permitted by the protocol were also considered treatment failures. The intention-to-treat analysis showed 70% positive results for the basic treatment and 29% for the treatment containing furfuryl palmitate (P < .0001) with a number needed to treat of 2.4 (95% confidence interval, 1.6-4.6). The emollient cream without furfuryl palmitate was observed to be more efficacious by pediatricians and parents, and no differences were reported between the 2 products in terms of tolerability. CONCLUSIONS: Both products proved to be efficacious in treating atopic dermatitis in children, but the emollient cream not containing furfuryl palmitate showed better clinical efficacy.

Predicting the outcome of oral food challenges with hen's egg through skin test end-point titration.

BACKGROUND: Oral food challenge (OFC) is the diagnostic 'gold standard' of food allergies but it is laborious and time consuming. Attempts to predict a positive OFC through specific IgE assays or conventional skin tests so far gave suboptimal results. OBJECTIVE: To test whether skin test with titration curves predict with enough confidence the outcome of an oral food challenge. METHODS: Children (n=47; mean age 6.2 +/- 4.2 years) with suspected and diagnosed allergic reactions to hen's egg (HE) were examined through clinical history, physical examination, oral food challenge, conventional and end-point titrated skin tests with HE white extract and determination of serum specific IgE against HE white. Predictive decision points for a positive outcome of food challenges were calculated through receiver operating characteristic (ROC) analysis for HE white using IgE concentration, weal size and end-point titration (EPT). RESULTS: OFC was positive (Sampson's score >or=3) in 20/47 children (42.5%). The area under the ROC curve obtained with the EPT method was significantly bigger than the one obtained by measuring IgE-specific antibodies (0.99 vs. 0.83, P<0.05) and weal size (0.99 vs. 0.88, P<0.05). The extract's dilution that successfully discriminated a positive from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256, corresponding to a concentration of 5.9 microg/mL of ovotransferrin, 22.2 microg/mL of ovalbumin, and 1.4 microg/mL of lysozyme. CONCLUSION: EPT is a promising approach to optimize the use of skin prick tests and to predict the outcome of OFC with HE in children. Further studies are needed to test whether this encouraging finding can be extended to other populations and food allergens.

[Testing a nutritional and taste education intervention approach to increase vegetables and fruit consumption among children]. / Intervento di Educazione Alimentare e del Gusto per in- crementare l'assunzione di ortaggi, legumi e frutta nei bambini.

The purpose of the study was to test a nutrition education intervention to promote a higher consumption of vegetables, pulse and fruit among children. The study involved 274 children of primary school (third and fourth grade). The sample was divided in three groups: A (exposed to intervention without taste education activities), B (exposed to intervention with taste education activities), C (control group not exposed to any intervention). Before starting the intervention on pupils, all teachers were properly trained and parents participated to informative/formative meetings. The teachers were also provided with didactic units to implement on children. The efficacy of intervention was evaluated by measuring food target not eaten at school lunch, before and after the implementation of intervention; it showed less plate waste for vegetables (side dishes) for both groups A and B (53.2% vs 44%) and (23.3% vs 8.1%) respectively, while for fruit only group A reduced to half its reject. The differences were however not significant. No increasing consumption was observed for soups or pasta prepared with vegetables or legumes. According to these preliminary results, we observed for some vegetable food items a better dietary behaviour trend among children of both groups who received the intervention compared with controls.

The inverse association of salmonellosis in infancy with allergic rhinoconjunctivitis and asthma at school-age: a longitudinal study.

BACKGROUND: Respiratory allergies are inversely related to early acquisition of food-borne and fecal-oral infections, consumption of unpasteurized milk, early exposure to stables and high endotoxin concentrations in a farming environment. We tested therefore if infection by Salmonella in early life can protect from development of respiratory allergies later in life. METHODS: During 2003, we studied two groups of Sardinian children (age 6-18 years) who had been hospitalized before 4 years of age (during 1989-2001) with non-typhoid salmonellosis (n = 148) or acute enteritis of nonbacterial etiology (NB-enteritis) (n = 167). Allergic rhinoconjunctivitis (AR) and asthma were evaluated by telephonic interview with a ISAAC questionnaire; participants reporting AR and/or asthma were further examined through a complete diagnostic work-up to objectively confirm or exclude current disease. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the role of different types of enteritis on the risk of developing allergic rhinoconjunctivitis or asthma over time. RESULTS: Children who had been hospitalized with salmonellosis had a lower prevalence of allergic rhinoconjunctivitis (eight of 148, 5.4%vs 23 of 167, 13.8%; P = 0.019) or asthma (five of 148, 3.4% vs 21 of 167, 12.6%; P = 0.006) than those who had been hospitalized with NB-enteritis. The proportional hazard of salmonellosis for asthma was 0.23 (95% CI: 0.08-0.67; P < 0.01) and for allergic rhinoconjunctivitis was 0.40 (95% CI: 0.17-0.95; P = 0.04), after adjusting for confounders. DISCUSSION: The strength of the observed associations suggests that Salmonella may contribute to shape the natural history of respiratory allergies. However, further studies are needed to test in other settings the association observed in Sardinian children. We speculate that clinical or subclinical infection by Salmonella may contribute to the atopy protective influence of a traditional farming environment or of areas endemic for food-borne and fecal-oral infections. Food hygiene and prevention of salmonellosis must remain however a public health priority.

Allergy, asthma and markers of infections among Albanian migrants to Southern Italy.

BACKGROUND: Studies of immigrants represent an useful tool to determine the relative relevance of environmental vs genetic factors in causing the reported rapid increase of the prevalence of sensitization and allergic diseases. METHODS: A total of 152 Albanian migrants to Southern Italy responded to a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and 139 of them underwent skin prick test, and 61 serological assays for total IgE and IgG antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV-1), hepatitis A virus (HAV) and Helicobacter pylori (HP). RESULTS: Reported asthma was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152; 15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%) subjects. The frequency of skin sensitization to pollen (P = 0.003) and that of hay fever (P = 0.004) increased with the time spent in Apulia. All the 61 sera had antibodies against HAV, 59/61 (96.7%) against HSV-1, 48/61 (78.7%) against HP and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever symptoms were correlated to the duration of residence in Southern Italy. CONCLUSIONS: Data presented indicate that Albanian migrants to Italy, in spite of the low prevalence of allergic diseases and sensitization in their country of origin, manifest with time an increasing prevalence of sensitization to local allergens and nasal symptoms after immigration to Italy. This would suggest a permanent role of allergen exposure and lifestyle factors in influencing the appearance of sensitization and symptoms of allergic diseases.

Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children.

BACKGROUND: It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children. METHODS: This was a case-controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests to 10 prevalent allergens at the time of examination. RESULTS: Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma. CONCLUSIONS: This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.

Efficacy of leuprorelin acetate depot in symptomatic fibromatous uteri: the Italian Multicentre Trial.

A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16-week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume to original size has been usual in most of the 82 patients now in follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of gonadotrophin-releasing hormone and related analogue on human luteal cell function in vitro.

The possible direct effect of gonadotrophin-releasing hormone (GnRH) and GnRH agonist (GnRH-A; buserelin) on basal and human chorionic gonadotrophin (HCG)-stimulated progesterone (P) and cyclic AMP (cAMP) production by cultured human luteal cells was examined. Luteal cells from the early or mid-luteal phase were incubated in long-term cultures. They responded to HCG stimulation with a 2- to 3-fold increase in P production and a 2-fold increase in cAMP production. The addition of GnRH (10(-7) and 10(-5) M) or GnRH-A (10(-7) and 10(-5) M) to the medium had no effect on either basal or HCG-stimulated secretion. These results indicate that both GnRH and GnRH-A have no direct effect on human luteal steroidogenesis in vitro.

A prostaglandin analogue (ONO-802) in treatment of missed abortion, intrauterine fetal death and hydatiform mole: a dose-finding trial.

Forty-eight patients affected with missed abortion, intrauterine fetal death and hydatiform mole were treated with vaginal suppositories containing 1 mg of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802). The patients were divided into two treatment groups. The first, Group A, was given one vaginal suppository every 3 h to a maximum of five suppositories. The product of conception was expelled in 95.8% of patients. In Group B the maximum number of suppositories was reduced to three. The product of conception was expelled in 100% of cases and the average duration of treatment was similar to that for the first group. Although side-effects were mild in both groups, they were reduced in the patients of Group B.

Fibrin glue vs. nylon in the anastomosis of rabbit fallopian tubes.

Fibrin glue was used in end-to-end tubal anastomosis on eight sexually mature female New Zealand white rabbits. The right fallopian tubes were anastomosed with 10/0 nylon and the left with fibrin glue (Tissucol). The animals were mated with males of proven fertility six weeks after surgery and killed two weeks later. The gestational sacs and corpora lutea on the right and left sides were counted separately and the nidation index calculated for each. The presence of adhesions was also evaluated. All the tubes were finally examined under a scanning electron microscope. The fibrin glue was satisfactory in terms of patency, pregnancy and morphology of the epithelium.