Fertility potential and safety assessment of residual ovarian cortex in young women diagnosed with epithelial borderline and early-stage malignant ovarian tumors.

OBJECTIVE: To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool. METHODS: Multicentric retrospective study of 48 subjects (15-45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68. RESULTS: Occult ovarian lesions were observed in 6 out of 45 cases investigated (14.6%), including one mucinous stage-I BOT (1/14), one serous stage-I BOT (1/13), 3 advanced-stage serous BOTs (3/11) and one early-stage serous EOC (1/7). Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors compared to controls (p < 0.001) and at a younger age. Significantly higher follicle atresia was encountered in the ovarian tumor group then in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. CONCLUSIONS: Personalized counseling for fertility preservation is required in the event of BOTs and early-stage EOCs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing the oncological risks according to tumor stage and histotype and fertility potential, especially at a younger age.

EWHETA (Eat Well for a HEalthy Third Age) Project: novel foods to improve the nutrition in the elderly people.

Cardiovascular diseases (CVD) are the leading cause of mortality. However, by treating modifiable cardiovascular risk factors and following a healthy diet as the Mediterranean diet, we have opportunity to prevent CVD. In the EWHETA (Eat Well for a HEalthy Third Age) Project, our goal has been to develop novel foods ("Mediterranean Lasagne", MLs) in versions all nutritionally complete and well balanced in terms of calories, whole carbohydrates, fibers, source of vegetable proteins, and vegetable fats. MLs can be easy prepared at home (inexpensively) and used as fresh food or can be pre-prepared and used in residences for elderly people or in health care residencies. The project has saw the alliance between nutritionists and food and sensor scientists and the active involvement of older people in tasting the novel foods to achieve the final tasty versions of the MLs. We think that the nutritional components of these novel foods and its well-accepted taste, insert in a healthy diet and life style (fundamental aspects at every age), and could contribute to improve diet in the elderly people and prevent malnutrition.

Invariant chain controls H2-M proteolysis in mouse splenocytes and dendritic cells.

The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii(-/-) mice. Downregulation reflects an increased rate of degradation in Ii(-/-) cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.

Hypokalemic periodic paralysis in a patient with acquired growth hormone deficiency.

CONTEXT: Hypokalemic periodic paralysis (HypoPP) is a rare disorder consisting of sudden episodes of muscle weakness with areflexia involving all four limbs, which spontaneously resolve within several hours or days. Primary HypoPP is genetically determined, while secondary acquired HypoPP has been described in association with thyreotoxycosis, hyperaldosteronism, kidney diseases, diuretics and liquorice abuse, gastrointestinal potassium loss, or cysplatinum therapy. OBJECTIVE: To report a case of HypoPP associated with GH deficiency. PATIENT: A 33 yr-old man with hypopituitarism and diabetes insipidus secondary to pituitary stalk-localized sarcoidosis, and documented HypoPP episodes. CLINICAL PRESENTATION: Neurologic exam outside HypoPP episodes was normal. Needle electromyography was normal without myotonia or other spontaneous electric activity. Muscle biopsy documented a vacuolar myopathy with tubular aggregates. However, genetic analysis ruled out common mutations of the voltage-gated calcium channel observed in primary HypoPP. Common causes of secondary HypoPP were also ruled out. The patient was diagnosed with severe GH deficiency with modest fasting hyperinsulinemia and insulin resistance and started on GH replacement therapy, an alpha-glucosidase inhibitor (acarbose) and a diet low in simple carbohydrates. CONCLUSIONS: GH replacement therapy, acarbose and a diet low in simple carbohydrates resulted in the complete long-term (>2 yr) remission of HypoPP episodes. This is consistent with the hypothesis that the hyperinsulinemia associated to GH deficiency may trigger HypoPP episodes by increasing Na+/K+ ATPase activity and K+ transport into the intracellular compartment with subsequent hypokalemia.

In vivo effect of human granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil GM-CSF receptors.

The effect of in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophils GM-CSF receptor, was investigated in patients with neoplastic diseases and normal hematopoiesis. Patients were divided into two groups. Group A received a single dose of rhGM-CSF (5 micrograms/kg/day) and receptor studies were performed 90 min and 48 h after treatment. Group B received three doses, administered subcutaneously every 24 h and receptor studies were performed 90 min after first injection and 24 h after the last. Before treatment neutrophils only displayed high-affinity receptors (KD 85 +/- 53 pM; number of receptors/cell 1318 +/- 567). The first injection of rhGM-CSF produced a transient leucopenia and the internalization of GM-CSF receptor on neutrophils in both groups of patients: 90 min after s.c. administration receptors could not be detected with conventional binding studies. In group A patients, 48 h after a single dose of rhGM-CSF, receptors, albeit with a decreased affinity (KD = 240 +/- 131 pM; number of receptors/cell 783 +/- 494) were again expressed. In group B patients, 24 h after the last rhGM-CSF injection, low intermediate affinity receptors not present before treatment appeared (KD 720 +/- 175 pM; number of receptor/cell 1222 +/- 179). They were associated with a low number of high affinity receptors (KD = 9 +/- 4 pM; number of receptors/cell 106 +/- 44). These observations indicate that more than one type of GM-CSF receptor may exist on neutrophils. It may be suggested that in vivo the regulation of the GM-CSF receptor is different from that in vitro and is related to the presence of the cytokine in patient blood.

Identification and characterization of homologues of the Exocyst component Sec10p.

The SEC10 gene product is a member of the Exocyst complex essential for exocytosis in the budding yeast Saccharomyces cerevisiae. We report here the cloning and characterization of human Sec10p (hSec10p; GenBank accession number U85946). hSec10p is a 77-kDa protein with 23% amino acid identity to yeast Sec10p and 37% identity to a C. elegans protein found in the database. Northern and Western blot analyses indicate that hSec10 has a broad tissue distribution. Immunofluorescence staining of COS cells cotransfected with hSec10p and a mammalian Sec8p demonstrates that these two proteins have an identical distribution in the cell including a localization in the peripheral cytoplasm. These data suggest that hSec10p is a component of the mammalian counterpart of the yeast Exocyst complex essential for post-Golgi traffic.

Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients.

Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk. The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet. Plasma total cholesterol was reduced with corn oil, but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive. Plasma apolipoprotein B levels were equally reduced by both diets; apolipoprotein AI and the apo AI:B ratio rose only with olive oil. Plasma-glucose levels were lowered significantly with olive oil. Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid (particularly with corn oil) and to collagen (particularly with olive). An olive oil diet with a moderate fat intake (about 30% of total calories) leads to favorable plasma lipoprotein and platelet changes.

Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia.

To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells, 12 type II patients were randomly allocated to three different diets, which provided polyunsaturated fatty acids (corn oil), monounsaturated fatty acids (olive oil), and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet. Olive oil and, more significantly, n-3 ethyl esters lowered total cholesterol best (-2.2% and -5.8%, respectively); the latter diet, as expected, also significantly lowered triglyceridemia (-21.4%). The corn-oil diet exerted a small, statistically significant reduction of high-density-lipoprotein cholesterol (HDL) (-4.3%), and it also lowered plasma total apo B concentrations (-3.8%). n-3 ethyl esters significantly raised both total (+3.1%) and particularly HDL2 cholesterol (+24%). Platelet reactivity was insignificantly reduced by the three regimens, but all three significantly reduced thrombin-stimulated formation of thromboxane B2. Finally, only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes. Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients, but significant differences may be found between the three tested regimens.

Clinical experience with the soybean protein diet in the treatment of hypercholesterolemia.

The efficacy of the total substitution of animal proteins with a textured soybean protein in hypercholesterolemic individuals was assayed in 42 in-patients and 18 out-patients. The in-patients studied followed one of three different crossover protocols: in protocol A, the soybean diet was compared with a standard low lipid diet; protocol B compared two soybean diets, one with added cholesterol, one without; and protocol C compared a soybean diet containing a high P/S fatty acid ratio to one with a low P/S ratio. In all three protocols, the soybean regimen provided valid and reproducible hypocholesterolemic effects that were not modified by the addition of cholesterol. P/S variations appeared, however, to modify the final effect: soybean definitely had a decreased effectiveness with a low P/S (0.1) regimen. The overall plasma cholesterol changes in the 42 in-patients after 3 weeks on the different soybean diet protocols was -20%. Patients with type IIA and IIB hypercholesterolemia provided almost equivalent results, whereas patients with mixed phenotypes (IIB-III) appeared somewhat more sensitive to the dietary effect. Cholesterol decreased mostly in the low density lipoprotein fraction, but some very low density lipoprotein changes were also noted upon variation of the P/S ratio. The out-patients studied provided less satisfactory results. possibly due to the difficulty of adequately complying with the diet. These studies indicate that treatment with the soybean diet is an effective regimen for inducing a significant cholesterol reduction in type II patients refractory to standard low lipid regimens.

Pharmacological studies on tiadenol in type IV patients. Evidence for a mechanism of action different from other lipid-lowering drugs.

Tiadenol [bis(hydroxyethylthio) 1-10 decane], a new absorbable hypolipidemic agent differing in chemical structure from clofibrate and related compounds, was tested in hypertriglyceridemic patients, both responsive and nonresponsive to dietary treatment. Tiadenol administration was remarkably effective in inhibiting fructose induced hypertriglyceridemia in diet responsive type IV patients; it was ineffective in patients with stable, diet refractory, hypertriglyceridemia. The significant reduction of plasma triglycerides (-42%) in sensitive patients, was not accompanied in this study, by the activation of plasma lipoprotein and hepatic lipases. In a second, longer term investigation of stable type IV patients, tiadenol administration resulted in significant triglyceride decreases in the very low density lipoproteins (VLDL) (-45%), as well as in the low and high density lipoproteins (LDL and HDL) (both -25%). The cholesterol content of LDL and HDL was not modified. In VLDL a significant reduction of apoprotein E was observed (from 15.2 +/- 4.9 to 11.9 +/- 5.9% of VLDL proteins). The reported observations are consistent with a difference in the mode of action of tiadenol from that of other lipid lowering agents, particularly of the clofibrate type.

Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet.

The fecal steroid elimination profile was studied in 7 type II hyperlipoproteinemic patients given a low-lipid diet with textured soybean proteins, in order to define the mechanism of the hypocholesterolemic activity of this new dietary regimen. Four of the patients followed a 3- + 3-week cross-over protocol, comparing the soybean diet with a reference low-lipid diet with animal proteins. In these, fecal neutral steroids and bile acids were analyzed by chromatography during the two dietary periods. In spite of the clear hypocholesterolemic effect, no significant differences in steroid output were noted between the two dietary periods. In the 3 remaining patients, a chromatographic + isotopic method (by injecting 14C-labelled cholesterol i.v. 4-6 weeks prior to the dietary study) was employed. Again, no marked changes were noted in the fecal neutral steroid and bile acid outputs and the slope of the decay curve of the plasma cholesterol-specific activity was not changed by the experimental diet, in spite of the remarkable decrease in plasma cholesterol. The reported results do not provide a definitive contribution to the mode of action of the soybean protein diet. They suggest, however, that it is not an effect mediated by undigestible dietary components. The possibility of a cholesterol redistribution from plasma to tissue pools should be considered.

Tnp-alpha determination in serum and pleural effusion in patients with lung-cancer.

The relationship between Tumor Necrosis Factor-alpha (TNF-alpha) in the serum and pleural fluid of lung cancer patients and the extent and the histological cell type was studied. TNF-(a)lpha level was determined in the serum of 68 patients with lung cancer [51 non-small cell lung cancer (NSCLC) and 17 small cell lung cancer (SCLC)] and in pleural fluid of 30 patients with lung cancer (22 NSCLC, 11 of them positive for neoplastic cells and 8 SCLC, 7 of them positive). Sera of 31 healthy subjects and the pleural fluid of 15 non-malignant pleural effusions were tested as controls. TNF-alpha serum level was increased in patients with lung cancer (healthy subjects 7.8+/-3.3 pg/ml; lung cancer 16.2+/-9.1 pg/ml), in NSCLC as well as SCLC and a relationship with the extent of the disease was found in both the histological types. In pleural fluid, no differences of TNF-alpha level were observed between neoplastic and benign inflammatory effusion, between SCLC and NSCLC or between cases positive and negative for the presence of neoplastic cells. Serum TNF-alpha may be an indicator of tumour burden; conversely, TNF-alpha in pleural fluid, was unable to discriminate between neoplastic and benign effusion.

Proposal for a new tomographic device providing information on the chemical properties of a body section.

A system to analyze the chemical properties of a region of tissue located deep inside the human body without having to access it is proposed. The method is based on a high precision detection of X-rays or gamma-rays (photons) from an external source Compton scattered from the tissue under inspection. The method provides chemical information of plane regions lying not too deep inside the body (<6 cm). The amount of radiation absorbed by the body is about the same as needed for a standard X-ray tomography. The exposure time is estimated to be shorter than 10 min.

Differential effect of unsaturated oils and butter on blood glucose and insulin response to carbohydrate in normal volunteers.

Plasma glucose and insulin responses were monitored in normal volunteers after a standard carbohydrate meal with unsaturated oils (olive and corn oil, in identical volumes) or butter. Both unsaturated oils almost totally blunted the glycaemic response; butter, instead, only delayed the plasma glucose rise, without significantly changing the area under the curve. The insulin rise was essentially unaffected by the three experimental meals, only a slight delay in the peak being observed with no differences between unsaturated oils and butter. These findings support previous data indicating reduced glucose levels after prolonged administration of olive oil, and reduced glycaemic response, in the absence of clear-cut insulin changes, differentiates unsaturated oils from indigestible fibres; it may be linked to an altered polysaccharide handling at the intestinal level.

EuCliD (European Clinical Database): a database comparing different realities.

Quality and variability of dialysis practice are generally gaining more and more importance. Fresenius Medical Care (FMC), as provider of dialysis, has the duty to continuously monitor and guarantee the quality of care delivered to patients treated in its European dialysis units. Accordingly, a new clinical database called EuCliD has been developed. It is a multilingual and fully codified database, using as far as possible international standard coding tables. EuCliD collects and handles sensitive medical patient data, fully assuring confidentiality. The Infrastructure: a Domino server is installed in each country connected to EuCliD. All the centres belonging to a country are connected via modem to the country server. All the Domino Servers are connected via Wide Area Network to the Head Quarter Server in Bad Homburg (Germany). Inside each country server only anonymous data related to that particular country are available. The only place where all the anonymous data are available is the Head Quarter Server. The data collection is strongly supported in each country by "key-persons" with solid relationships to their respective national dialysis units. The quality of the data in EuCliD is ensured at different levels. At the end of January 2001, more than 11,000 patients treated in 135 centres located in 7 countries are already included in the system. FMC has put the patient care at the centre of its activities for many years and now is able to provide transparency to the community (Authorities, Nephrologists, Patients.....) thus demonstrating the quality of the service.

Comprehensive case management in the private sector for patients with severe mental illness.

Intensive case management for severely psychiatrically ill patients is a relatively new phenomenon in the private sector. The authors describe a comprehensive case management program designed at Blue Cross Blue Shield of Massachusetts to meet the needs of the most severely ill psychiatric patients in a private managed care environment. The case management program emphasizes involvement of patients in creating comprehensive treatment plans; development of a relationship between case managers, patients and their families, and providers; and clinical coordination between the public and private sectors to create individualized treatment plans. The program's case managers are able to flex the benefit limitations of a managed care or indemnity plan to integrate public and private services and can enlist providers outside a managed care network. The paper describes service utilization by the first 33 patients who participated in the program for one year.

EuCliD--a medical registry.

OBJECTIVES: The European Clinical Database EuCliD small star, filled has been developed as a tool for supervising selected quality indicators of about 200 European dialysis centers. Major efforts had to be made to comply with local and European laws regarding data security. METHOD: EuCliD is a Lotus Notes based flat-file database currently containing medical data of more than 14,000 dialysis patients from 10 European countries. Another 15,000 patients from 150 centers in 4 South-American countries will be added soon. Data are entered either manually or by means of interfaces to existing local data managing systems. This information is transferred to a central Lotus Notes Server. Data evaluation was performed with statistical tools like SPSS. RESULTS: EuCliD is used as a part of the CQI (Continuous Quality Improvement) management system of Fresenius Medical Care (FMC) dialysis units. Each participating dialysis center receives (currently every half year) benchmarking reports at a regular interval. The benchmark for all quality parameters is the weighted mean of the corresponding data of all centers. CONCLUSIONS: An obvious impact of data sampling and data evaluation on the quality of the treatments could be observed within the first one and a half years of working with EuCliD. This also concerns important outcome predictors like Kt/V and hemoglobin concentration as the outcome itself expressed in hospitalization days and survival rates. With the help of EuCliD the user is able to sample clinical data, identify problems, search for solutions with the aim of improving the dialysis treatment quality and guarantee a high-class treatment quality for all patients.

Plasma amino acids changes in obese patients on very low-calorie diets.

The reduced feeling of hunger alleged by obese patients on very low-calorie diets (VLCD) could be supposed due to restoration to a normal level of plasma TRP:LNAA ratio, previously found lowered in these subjects. We tested this hypothesis measuring weekly the changes of plasma amino acid concentration in obese individuals who followed a 5 week slimming regimen consisting in a powdered formula diet (500 kcal/d). A decrease in plasma TRP:LNAA ratio was seen, since tryptophan decreased, whereas valine and isoleucine increased over time. An increase in plasma lysine, threonine, glycine and aminobutyrate was also observed. The early decrease shown by alanine and glutamate was followed by an increase in the last weeks of the study. Our hypothesis was not confirmed, since VLCD failed to carry back the plasma TRP:LNAA ratio to a normal level.

In vivo recording of blood velocity profiles and studies in vitro of profile alterations induced by known stenoses.

Recordings of blood velocity profiles and their behavior in the time domain in some peripheral human vessels (carotid arteries and limb vessels) are reported. Measurements have been obtained with a pulsed ultrasonic instrument based on the analysis of the cross-correlation function of blood-diffused echoes. The alterations of blood velocity profiles and of the velocity in the time domain, induced by known stenosis, have been studied in vitro as a function of the distance between stenosis and measuring point, and the position of the sample volume along the diameter. These studies may be useful for a better comprehension of blood velocity measurements made with ultrasound equipment for clinical noninvasive diagnostic purposes.

[Ambulatory treatment of obesity with modified fasting (Modifast)]. / Il trattamento ambulatoriale dell'obesità con il digiuno modificato (Modifast).

52 obese subjects, 17 to 65 years old, 42.5 +/- 23.37 percent mean body weight excess, were treated with a very low-calorie diet (1020 KJ = 240 Kcal/day), containing whole egg protein (g 33), disaccharides (g 25.5), vitamins and minerals (Modifast). The diet was well tolerated by all subjects, without important side effects, and the following significant mean weight losses were registered: -kg 3.4 +/- 1.1 after 1 week (52 subjects); -kg 5.4 +/- 1.4 after 2 weeks (38 subjects); -kg 8.7 +/- 1.4 after 4 weeks (20 subjects); -kg 11.8 +/- 1.6 after 6 weeks (7 subjects); -kg 17.3 +/- 0.8 after 10 weeks (2 subjects); -kg 20.4 after 13 weeks of treatment (1 subjects). A significant reduction of plasma glucose, cholesterol and triglycerides were detected at the end of the dietary treatment, in contrast plasma uric acid concentration rose significantly but within the normal limits. Modified fasting with protein-carbohydrate supplementation (Modifast) may be successfully and safely prescribed also to obese out-patients, provided a careful patient selection, a weekly clinical and biochemical examination and a daily potassium supplementation (20-30 mMol) are performed.