Predictive factors in in-vitro maturation in unstimulated women with normal ovaries.

The in-vitro maturation protocol (IVM) is an intriguing tool in assisted reproduction since it omits the side-effects of drug stimulation and reduces the cost of the entire procedure, both in terms of time and patient/society costs. In the Biogenesi Reproductive Medicine Centre, the IVM technique has been applied for more than 3 years, obtaining successful results in terms of maturation and fertilization rates, number of pregnancies and healthy babies born. At present, IVM is widely accepted in polycystic ovary and polycystic ovarian syndrome patients but its application in other women is still controversial. This study has been carried out in order to determine the efficiency of unstimulated IVM in women with morphologically and endocrinologically normal ovaries. Body mass index, basal FSH and oestradiol concentrations, antral follicle count, endometrial thickness and lead follicle size were correlated with the outcome of the procedure so as to obtain useful criteria to select women with regular cycles for an IVM technique. It was found that basal oestradiol concentration, FSH concentration and antral follicle count are useful criteria in deciding whether to start and continue the procedure, while lead follicle size and endometrial thickness are important criteria in deciding the timing of oocyte retrieval.

Human oocyte cryopreservation: comparison between slow and ultrarapid methods.

The success of reproductive technologies is facilitated by the cryopreservation of embryos and gametes. In Italy, where legislation prohibits zygote and embryo cryopreservation, clinics have extensively introduced oocyte cryopreservation. Two different strategies of oocyte cryopreservation are available: slow freezing or ultrarapid cooling (vitrification). Although the results are very encouraging with both methods, there is still controversy regarding both the procedure itself and the most suitable method to use. This study reports the routine application of the two different oocyte cryopreservation methods in programmes running in two consecutive periods. The study centre carried out 286 thawing cycles for a total of 1348 thawed oocytes cryopreserved by the slow-freezing method and 59 warming cycles for a total of 285 warmed oocytes cryopreserved by vitrification. Comparison of the outcomes obtained with the slow-freezing method versus vitrification in women who underwent IVF for infertility showed survival, fertilization, pregnancy and implantation rates of 57.9% versus 78.9% (P < 0.0001), 64.6% versus 72.8% (P = 0.027), 7.6% versus 18.2% (P = 0.021) and 4.3% versus 9.3% (P = 0.043) respectively. These results suggest that oocyte vitrification is associated with a better outcome than the slow-freezing method.

Effect of different gonadotrophin priming on IVM of oocytes from women with normal ovaries: a prospective randomized study.

This study was designed to determine if the efficiency of in-vitro maturation (IVM) in women with normal ovaries can be improved by gonadotrophin administration. 400 women were randomly allocated in four groups: group A, non-primed cycles; group B, human chorionic gonadotrophin (HCG)-primed cycles; group C, FSH-primed cycles; and group D, FSH- plus HCG-primed cycles. There were significant differences in the IVM rate among the groups. In groups where HCG was used, the overall maturation rate was higher (57.9% in group B and 77.4% in group D; 48.4% in group A and 50.8% in group C) and the percentage of total available metaphase II-stage oocytes was higher (60.4% in group B and 82.1% in group D; 48.4% in group A and 50.8% in group C). The overall clinical pregnancy rate per transfer (CPR) was 18.3% and the implantation rate (IR) was 10.6%. There was a difference in CPR among the groups: group D (29.9%) versus group A (15.3%), P = 0.023; group D versus group B (7.6%), P < 0.0001; group D versus group C (17.3%), P = 0.046. The results of this study are clearly in favour of FSH plus HCG priming. FSH priming and HCG priming alone showed no significant effects on clinical outcome.

Relationship of insulin binding and insulin-stimulated tyrosine kinase activity is altered in type II diabetes.

The insulin receptor contains an alpha subunit with insulin binding properties and a beta subunit with insulin-stimulated tyrosine kinase function. Preparations containing insulin and insulinlike growth factor I (IGF-I) receptors were obtained from solubilized human red cell membranes by affinity chromatography. After separate assays for insulin binding and insulin-stimulated tyrosine kinase activities, a high degree of correlation was found between these activities in preparations from normals and diabetics. Identical studies using IGF-I as the ligand showed a lesser degree of correlation. We compared 24 normal subjects and 14 untreated type II diabetics and found significant diminution in the slope of the line coupling insulin binding and insulin-stimulated kinase activities in the diabetics. This difference was not observed in a similar study of IGF-I-related activities. Compared to normal controls, untreated type II diabetics have reduced tyrosine kinase activity stimulated per unit insulin binding.

Expression of peptide hormone genes in human islet cell tumors.

The embryogenesis of the pancreas suggests the existence of a common stem cell progenitor of the four islet cell types (insulin, glucagon, somatostatin, and pancreatic polypeptide). We investigated whether neoplastic islet tumors express multiple hormone-specific cellular phenotypes of the islets. By analyses of RNA transcripts and immunoreactive peptides in four human insulinomas and one glucagonoma, we found that the insulin, somatostatin, and glucagon genes were coexpressed in all tumors. The expression of the three hormone genes in a lymph node metastasis of a glucagonoma reduced the possibility that contamination of tumor tissue by normal islets occurred. These observations lend further support to the hypothesis of the multipotentiality of neoplastic islet cells for the expression of genes encoding several different islet hormones.

The response of serum growth hormone levels to the long-acting somatostatin analog SMS 201-995 in acromegaly.

SMS 201-995 (SMS) is a long-acting analog of somatostatin. We studied the effect of SMS (50-100 micrograms, sc, every 8 h) on serum GH in five patients with acromegaly. Serum GH decreased significantly in four of the five patients 4 h after SMS treatment. In two of the four patients, this reduction was not sustained for 7 h, but sustained reduction to normal GH concentrations did occur in the two patients who had basal serum GH levels below 15 ng/ml. In the two patients whose responses were not sustained for 7 h, a higher dose of SMS did not cause sustained reduction in GH. SMS was well tolerated, except for one episode of elevated serum aminotransferase levels. These results indicate that SMS-induced reductions in serum GH in patients with acromegaly are often not sustained despite SMS administration every 8 h and indicate that the insufficient duration of effect may limit its therapeutic efficacy.

Tyrosine kinase activity of the insulin receptor of patients with type A extreme insulin resistance: studies with circulating mononuclear cells and cultured lymphocytes.

The syndrome of type A insulin resistance in nonobese women is characterized by hyperinsulinemia, resistance to exogenous insulin, acanthosis nigricans, polycystic ovaries, and masculinization. Insulin binding to intact circulating monocytes and cultured Epstein-Barr virus-transformed B-lymphocytes derived from these patients is decreased in some patients but normal in others. Insulin receptors consist of two subunits; the alpha-subunit contains the insulin-binding site, and the beta-subunit possesses an insulin-sensitive tyrosine-specific protein kinase activity. Insulin binding to circulating monocytes was decreased in five patients, suggesting a decreased number of alpha-subunits on the surface of cells from the patients with type A insulin resistance. In the present work, we demonstrated that there is a proportional decrease in the function of the beta-subunit (i.e. tyrosine kinase activity) in cells from these subjects. In one patient, insulin binding to circulating monocytes was normal, and the insulin-stimulated tyrosine kinase activity of the receptors was normal as well. In separate studies, using cultured Epstein-Barr virus-transformed lymphocytes from the same six patients with type A extreme insulin resistance, the results were similar, in that the functions of the alpha- and beta-subunits of the receptor from these cells correlated. Though heterogeneity among the six patients with type A extreme insulin resistance at the level of the kinase activity of their insulin receptors was demonstrated, it does not appear that a selective defect in beta-subunit phosphorylation per se can be implicated in the mechanisms of insulin resistance of these patients. These findings are distinct from our previously reported patient with normal binding and very low insulin-stimulated phosphorylation of the beta-subunit of the receptor of circulating monocytes, in whom it was speculated that selective reduction in beta-subunit phosphorylation was responsible for insulin resistance.

Approach to acute hypoglycemia.

Hypoglycemia is a common clinical disorder with a large number of possible causes. Hypoglycemia is defined for the clinician as a diagnosis rather than a symptom complex. Hypoglycemic states can be characterized initially as medication associated, fasting, or postprandial. An approach based on the physiologic mechanisms that support euglycemia is useful to sort through the differential diagnosis of hypoglycemia for both adults and children.

Efficacy of insulin pump therapy: mealtime delivery is the key factor.

OBJECTIVE: To investigate, in a clinical setting, the effect of implementation of continuous subcutaneous insulin infusion (CSII) on control of plasma glucose and to identify factors associated with improved glycemic control in patients with type 1 diabetes mellitus. METHODS: Nineteen patients (16 women and 3 men) with type 1 diabetes were studied retrospectively. Their mean age was 42.6 years (range, 30 to 58), and the mean duration of diabetes was 21 years. The subjects underwent follow-up for a mean of 14 months after conversion to CSII therapy. With use of paired t tests, pre-CSII and follow-up data were evaluated relative to changes in weight, insulin dosing, and glycosylated hemoglobin (HbA(1c)). RESULTS: At follow-up, the total daily dose of insulin had decreased by 18%, from a baseline mean value of 45.2 IU to 37.1 IU (P = 0.02). HbA(1c) was reduced from 8.4% to 7.7% (P<0.01). The total daily insulin-to-weight ratio also significantly decreased from 0.66 IU/kg to 0.53 IU/kg (P<0.05). Before insulin pump use, the regular/NPH insulin ratio was 0.5 IU; at follow-up, the pump bolus/basal insulin ratio was 1.0 IU (P = 0.02). No weight gain was observed; the mean weight of the study patients decreased 0.2 kg, from 69.4 kg at baseline to 69.2 kg at follow-up (not significantly different). CONCLUSION: In a clinical setting, CSII therapy in patients with type 1 diabetes improves glycemic control and lowers the total daily basal insulin dose without affecting weight. Improved glycemic control was associated with a shift in insulin therapy from a high percentage of intermediate-acting insulin to a greater percentage of insulin administered in a meal-associated bolus form. This study emphasizes the importance of mealtime insulin adjustment for tight glycemic control in patients using CSII therapy. Future studies evaluating the benefits of decreased total insulin and an increased bolus/basal insulin ratio may be important in helping to understand how to avoid long-term complications of diabetes.

A unique collaborative network for diabetes education.

The DCNH is a unique collaborative venture in outpatient diabetes education. We believe it can serve as a model for rapidly developing standardized diabetes education in geographically dispersed communities. The heart of the organization is the educators' meeting, which enables an extensive sharing of ideas and information that benefit all patients in the region. The features crucial to our success have been (1) administrative leadership with a nursing management or educator background, (2) data collection and analysis, (3) local development of an educational curriculum based on ADA standards, and (4) centralized medical and administrative directors who are available to meet individual program needs. However, we are most indebted to the farsighted and strong commitment of our member hospitals to diabetes care in their communities.

Octreotide: a hormone for all diseases?

Octreotide is a new agent with many documented useful applications and a huge number of possible applications. Each documented therapeutic effect will require careful analysis. Particular care must be taken to design controls, use double-blind tests for objective study of subjective benefits, and frame questions to elicit precise answers. The most important guide is to keep an open mind when attempting to discern a mechanism of action.

[The food poisoning problem in communal restaurant facilities]. / Il problema delle tossinfezioni alimentari nelle strutture di ristorazione collettiva.

In view of the considerable development during the last few years of communal feeding facilities (factory, school, and university canteens, hospital kitchens, self service, fast food, and restaurants) in our country as well as elsewhere, the authors wish to supply detailed information on the incidence of food poisoning in Italy from 1979 to 1988 in such facilities. They report the findings of an epidemiological study they carried out in Rome and Lazio [correction of Latium] covering this period and which by and large confirmed the trend observed at the national level. As to prevention, the most recent techniques for food conservation are described.

[Minor salmonellosis in childhood: epidemiological and preventive considerations]. / Salmonellosi minori in età pediatrica: considerazioni epidemiologiche e preventive.

The diffusion of so-called minor salmonellosis in Italy, 18,135 isolates in 1985 -and the serious illness that they may induce in correlation to age and state of health have moved the Authors to consider their epidemiology and discuss their prevention. The morbidity per 100,000 population, from about 10 in the early '70s, has grown to a peak of 22.22 in 1976 and, after having irregularly reduced to a value of 16.76 in 1984, has grown again to 22.23 in 1986. Travelling abroad, modern breeding technologies, animals and raw food trade among States are frequently indicated as the most important factors in spreading salmonellas. The rise of morbidity in Italy has indeed occurred in concomitance with the renewal of breeding activity realized by means of animals imported from abroad, and moreover, presence of strains of S. typhimurium identical to those which caused serious epidemic outbreaks in bovine and humans in Great Britain and other Countries of North Europe is now ascertained. Recently, cooked ham prepared with raw meat contaminated with two serotypes uncommon in Italy (S. corvallis and S. mbandaka), imported from Rumania and Holland, has been the cause of two foodborne outbreaks each showing both of the above contaminants. At present, salmonellosis is quite common in large urban areas and is supported by person-to-person spread; more than 50% of the yearly isolates occurs in childhood Number of cases, their ages, sex distribution, and relative morbidity, have been calculated in Tab. 1, 2, 3, 4. From 1976 to 1986 the withdraw of S. wien, the research of excretors, and the improvement of quality of life, are all factors that may have favoured the lowering of morbidity at age zero, while the increasing of the same index at the ages 1-5 and 6-10 may correlate to the high number of serotypes of Salmonella now endemic in Italy. The diffusion of fast-food and the habit, recently acquired in our Country, to buy at shop cooked foods ready to eat, may be involved too. Age distribution shows a highest number of isolates at age zero and a still high number at ages 1, 2, and 3. Throughout childhood morbidity is lower in females. From 1975 on, the percentage increase of number of children admitted for minor salmonellosis is also indicated by surveys held at many Hospitals in Italy.(ABSTRACT TRUNCATED AT 400 WORDS)

[Ocular diseases in public health]. / Le patologie oculari: aspetti attuali di sanità pubblica.

The renewed sensibility towards the quality of life of disability has moved the authors to undertake a review to assess the low vision-blindness phenomenon as a public health problem. Particular attention has been paid to the aetiology and to the geographic distribution worldwide and in Italy. The prevention aspects of the main ocular diseases widespread in the industrialized countries, including the interventions focused on the patient and on the rehabilitation, have been analysed.

[Noise and communal dining facilities]. / Rumore e ristorazione collettiva.

Noise is a sound which is unwanted, either because of its effect on humans, its effect on fatigue or multifunctions of physical equipment, or its interference with the perception or detection of other sounds. It is a part of environmental pollution which can, in certain circumstances, reach worrying levels for the population (130 dB cause pain). Unsuitable exposure to noise for even short periods of time is responsible for symptomology involving the hearing organs (hypoacusis) and other parts of the body such as the cardiovascular, muscular and digestive systems via the connection between the central and the autonomous nervous systems. Noise in communal eating areas can be classed as coming from 3 sources: 1) operation of cooking machinery; 2) banging of pans and equipment; 3) voices of both staff and diners. The intensity of noise on these premises varies generally between 60 and 80 dB (discomfort threshold). The Regulations governing this subject are D.Lgs n.277 of 15/8/1991 regarding the protection of employees, D.P.C.M. of 1/3/1991 which establishes the maximum levels of noise both in the home and outside, and the more recent D.P.C.M. of 21/5/1999 referring to noise in public places, which includes restaurants. To contain the exposure to noise in public eating places, we believe that action should be taken at legal levels with stricter limits than the recently passed level of 105 dB, in the building planning departments and also with technological intervention in order to reduce the effects that noise has on the auditive and extra-auditive organs and thus limit possible sublimal messages which certainly do not benefit the psycho-physical well-being of the diners.