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Biomedical subjects

F Lombardo

Publications and source records attributed to F Lombardo.

At least 37 records · Page 2Linked to original sources

Nutritional, glycometabolic and genetic factors affecting menarcheal age in cystic fibrosis.

Aims of this study were to investigate menarcheal age (MA) and menarcheal determinants in 25 girls with cystic fibrosis (CF) and to compare their MA with their respective mothers'. Patients' MA (13.3 +/- 1.1 yr) was on average significantly higher (p<0.0005) than that of the respective mothers (12.2 +/- 1.0 yr) and positively related to it (r=0.055, p<0.005). Six girls experienced menarche after 14.2 yr, ie after the uppest limit of their mothers' MA range. The only parameter which significantly differentiated these 6 patients from the remaining 19 cases was body mass percentile (BMP). Moreover, in the entire patient series a negative correlation was found between MA and BMP. None of the other clinical parameters correlated significantly with MA. No differences in terms of MA were detected in the subgroups of patients with a different glucose tolerance (GT) status and the 12 girls with a pathological GT were not older at menarche than those with normal GT. No correlations were found between either glucose or insulin areas during oral GT test and MA. In the subgroups of patients with a different genotype menarche occurred at a similar age, irrespectively of their genotype. On the basis of our findings we conclude that: a) a menarcheal delay of approximately 1 yr exists between CF girls and their mothers; b) menarcheal delay in CF is not related to either genotype or disease severity or glycometabolic status; c) the only two factors which are able to affect MA in CF are maternal MA and nutritional status.

Adolescent↗

Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia.

OBJECTIVE: The loss of pancreatic beta-cells is thought to be one of the principal causes of diabetes mellitus (DM) in cystic fibrosis (CF), but the role of peripheral insulin resistance (IR) in the pathogenesis of DM in CF remains unclear. The aim of this study was to evaluate whether eventual changes of glucose tolerance (GT) over time were associated with modifications of insulin secretion or sensitivity. METHODS: Plasma glucose and insulin responses to an oral GT test (OGTT) were investigated and reinvestigated 13 Years later in 14 CF patients with initial and persistent fasting euglycemia and no history of insulin treatment. Insulin sensitivity (IS) at both tests was assessed on the basis of insulin and glucose levels both in the fasting state and during OGTTs. RESULTS: From the 1st to the 2nd OGTT: (a) the prevalence of DM responses significantly increased; (b) the areas beneath the respective glucose and insulin curves significantly increased and decreased respectively; (c) IR and IS indices decreased and increased respectively, even in the patients who developed DM; (d) pulmonary function significantly worsened in the entire series, especially in the patients who developed DM. CONCLUSIONS: (i) the natural history of glyco-metabolic status in CF is characterized by deteriorating GT over time; (ii) insulinopenia plays a prominent role in the pathogenesis of GT worsening; (iii) IR does not play any significant part in the pathogenesis of DM development; (iv) deterioration of lung function tests is more severe in the subjects who develop DM over time.

Adolescent↗

Stress, sexual dysfunctions, and male infertility.

Involuntary childlessness is considered to be a chronic stressor for couples suffering from infertility. Stress itself may interfere with spermatogenesis and fertility rate. The long period of diagnostic and treatment procedures may also have a negative impact on the sex life of the infertile couple. In fact, we observed in such patients a higher frequency of male sexual disturbances expressed as erectile dysfunction, ejaculatory disorders, loss of libido and a decrease in the frequency of intercourse. We tried to partially overcome these sexual symptoms by administration of 50 mg of a type-V phosphodiesterase inhibitor (sildenafil) to two selected groups: patients collecting semen for artificial insemination and male partners of couples before post-coital testing. The results of this uncontrolled pilot study suggest that sildenafil is effective in increasing compliance of male patients facing infertile couple management procedures, and also in improving some sperm parameters, above all the number of sperm penetrating the cervical mucus.

Humans↗

Endocrinological diagnosis in sexology.

Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinemia, but almost all extra-gonadal endocrinopathies (hyper- and hypothyroidism, hyper- and hypocortisolism, steroidal secreting tumors, etc.) may play a role to a greater or lesser extent in sexual function. It is therefore necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are usually extremely responsive to medical or surgical therapy.

Endocrine System Diseases↗

Liver glycogenosis as early manifestation in type 1 diabetes mellitus.

Clinical symptoms and biochemical findings related to liver dysfunction are not generally reported among the presentation features of Type 1 diabetes mellitus (T1DM) in infancy and childhood. To our knowledge this is the first paper reporting two children with a clinical and biochemical picture of hepatic glycogenosis at the presentation of T1DM. In both cases at beginning of insulin therapy liver function and dimensions were absolutely normal, even though glycometabolic status had been severely altered for many days at T1DM onset. Both hepatomegaly and aminotransferase abnormalities were first found only some days after the institution of treatment with supraphysiological insulin doses. In both patients the improvement of glycometabolic control under insulin therapy was followed within some weeks by a complete physical and biochemical recovery, as typically reported in hepatic glycogenosis. These case reports demonstrate that hepatic glycogenosis can occur at any stage of T1DM and may even be one of its earliest manifestations, together with those classically reported at the onset of T1DM. Since long-standing hyperglycaemia and overinsulinisation are metabolic pre-requisites for hepatic glycogen storage, liver glycogenosis should be expected to be not uncommon during the first phases of T1DM, especially in the cases who are initially treated with supraphysiological insulin doses.

Adolescent↗

Three-year prospective evaluation of glucose tolerance, beta-cell function and peripheral insulin sensitivity in non-diabetic patients with thalassemia major.

The aim of this prospective study was to evaluate the evolution of glucose tolerance (GT), insulin secretion and peripheral insulin sensitivity during a 3-yr follow-up in a homogenous population consisting of fourteen non-diabetic adults with thalassemia major (TM). All the patients underwent 2 OGTTs with a 3-yr interval and random measurements of fasting glycemia during the entire follow-up. At the time of both OGTTs, peripheral insulin sensitivity was assessed by both homeostatic model assessment (HOMA) index and a novel index derived from the OGTT. At the second OGTT patients exhibited both significantly higher fasting glucose concentrations and enhanced glycemic responses, with greater average glucose areas. GT deterioration over time was accompanied by a reduction of insulin sensitivity, with no concomitant change of insulin secretion. No patient developed diabetes mellitus (DM) during follow-up. To conclude, the natural history of glycometabolic status in TM adults seems to be characterized by a GT deterioration over time, which may probably reflect an increase of insulin resistance. GT deterioration is more evident in patients with the highest responses to the 1st OGTT and particularly in those with pre-existing impaired GT.

Adult↗

Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: from basic to clinic.

The lipid metabolism in sperm cells is important both for energy production and for cell structure. A special composition of membrane phospholipids, rich in polyunsaturated fatty acids (PUFA), and the different composition of sperm and immature germ cell membrane are described and discussed. Testis germ cells as well as epididymal maturing spermatozoa are endowed with enzymatic and non-enzymatic scavenger systems to prevent lipoperoxidative damage. Catalase, superoxide dismutase, and glutathione-dependent oxidoreductases are present in variable amounts in the different developmental stages. Phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity and roles in caput and cauda epididymal sperm cells are discussed. Also seminal plasma has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation and the degree of PUFA insaturation acts to achieve the same goal. Systemic predisposition and a number of pathologies can lead to an anti-oxidant/pro-oxidant disequilibrium. Scavengers, such as glutathione can be used to treat these cases as they can restore the physiological constitution of PUFA in the cell membrane.

Animals↗

A cluster of four D7-related genes is expressed in the salivary glands of the African malaria vector Anopheles gambiae.

Four genes expressed in the Anopheles gambiae adult female salivary glands and similar in sequence to the Aedes aegypti D7 gene were identified. The genes, called D7-related (D7r), are included in a single cluster encompassing approximately six kilobases on chromosome arm 3R. The deduced proteins contain secretory signals and they are probably injected by the mosquito into the host with the saliva during blood feeding. The region of similarity to D7 encompasses the carboxy-terminal part of the Ae. aegypti protein and the different An. gambiae D7r show a degree of similarity to each other, varying from 53% to 73%. The weak but significant similarity to members of a wide family of insect proteins, including odourant- and pheromone-binding proteins, raises the possibility that the D7r-encoded proteins may bind and/or carry small hydrophobic ligands.

Aedes↗

Endoscopic treatment of esophageal granular cell tumors.

There are no standard guidelines for the treatment of granular cell tumor (GCT). The aim of our study was to describe three cases of esophageal GCT and, on the basis of our experience, analyze the indications for and results of their endoscopic treatment. When deciding whether to proceed with surgical or endoscopic resection, endosonography plays a key role in establishing whether the tumor is confined to the submucosa. All three cases were confined within the hyperechoic layer of the submucosa and were successfully treated by endoscopic excision without complications or signs of relapse during the follow-up period.

Adult↗

Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer.

BACKGROUND AND STUDY AIMS: The aims of this study were to identify risk factors for recurrence of hemorrhage in bleeding gastroduodenal ulcers after endoscopic injection therapy, and to develop a simple and relevant prognostic score which could be used to assess the early risk of recurrence and the residual risk of rebleeding. PATIENTS AND METHODS: A prospective study was conducted from January 1995 to December 1998, in 738 patients who were admitted to our department for acute bleeding peptic ulcer and who underwent endoscopic examination. Ulcers with active bleeding or signs of recent bleeding were treated with injection therapy using epinephrine (1/10,000) and 1% polidocanol. RESULTS: Multivariate analysis revealed that liver cirrhosis, recent surgery, systolic blood pressure below 100 mmHg, hematemesis, Forrest classification, and ulcer size and site were significantly predictive variables for the recurrence of hemorrhage. Among these, Forrest classification was the most important. The overall accuracy of the predictive model was 71% (95% CI = 63 - 79%). The model showed a better sensitivity of 90% for early rebleeding (< 48 hours) than for late rebleeding (> or = 48 hours) where the sensitivity was 65 %. A prognostic score was obtained and patients were classified into four risk classes: very low (VL), low (L), high (H), and very high (VH). The rebleeding rates for the four classes were 0%, 7.9%, 31.8% and 67.9%, and the mortality rates were 5.9%, 8.6%, 13.9% and 35.7%, respectively. The residual risk of rebleeding after 48 hours was 0%, 3.3%, 10.4%, and 14.3% in the VL, L, H and VH classes, respectively. After 5 days the residual risk was under 4% in all classes. CONCLUSIONS: This study demonstrates that the proposed prognostic score, which is easily obtained after emergency endoscopy, is useful in clinical practice because it can identify patients with different levels of rebleeding risk. It can be helpful in patient management and decision making for discharge.

Aged↗

[Peptic ulcer hemorrhage in the elderly].

BACKGROUND: The aim of this study was to investigate the efficacy of endoscopic injection therapy on the clinical outcome of elderly patients with peptic ulcer bleeding. METHODS: From January 1995 to December 1998, 738 patients with acute peptic ulcer bleeding were observed in the First Division of General Surgery, University of Verona: 359 aged <70 years and 379 =/>70 years. History, clinical and endoscopic findings and outcome were prospectively collected and analyzed comparing old (=/>70 yrs) and young (<70 yrs) patients. Ulcers with active or sign of recent bleeding were submitted to injection therapy using epinephrine and 1% polidocanol. RESULTS: Coexisting diseases were significantly more present in the elderly group except for liver cirrhosis that affected preferentially young patients (12.3 versus 4.0%; p<0.001). Endoscopic treatment was performed in a similar percentage between young and elderly patients (respectively 64.9 e 61.5%) and also the rebleeding rate (14.2 versus 13.2) and the mean duration of hospitalisation were not different. The overall mortality was 12.7% in the elderly group and 8.3% in the young group (p=0.04), whereas mortality after surgery was significantly higher in the young group (respectively 57.1 versus 8.3%; p=0.037). CONCLUSIONS: The clinical and endoscopic features and reebleeding rate were not different between elderly and young patients. Patients aged 70 years or older have a higher number of associated medical diseases except for liver cirrhosis conditions and a highest overall mortality whereas the risk of death after surgery is lower than in the younger group.

Acute Disease↗

Interventional treatment of sialoliths in main salivary glands.

PURPOSE: The aim of our study was to demonstrate the effectiveness of interventional radiology in the treatment of sialolithiasis, as the first-choice treatment for the removal of stones located in the middle and proximal tracts of the main salivary ducts, and to assess its limitations and contraindications. MATERIAL AND METHODS: Between February 1998 and May 2001 eleven interventional removals of sialoliths were performed for recurrent obstruction of the main salivary duct associated with chronic sialadenitis. Patients were selected on the basis of a preliminary sialogram, designed to determine the location and size of the stone. Exclusion criteria were location of the stone in the gland hilum or intraglandular stone, maximum stone diameter >20% of the duct calibre, signs of adherence of the stone to the duct wall. Stone removal, performed after obtaining informed consent, involved administering antibiotic therapy and local anaesthesia, and dilatating the duct ostium to enable introduction of the basket catheter. The basket was then advanced along the duct under fluoroscopic guidance and suitably manoeuvred so as to capture and extract the stone. On completing the procedure a sialogram was taken to ensure the complete patency of the duct. Patients were prescribed a short course of antibiotics and were followed up at 1, 3 and 6 months. RESULTS: In 10/11 patients the stone was located in Wharton's duct and in 1/11 in Stensen's duct. Removal of the calculus was successful in 10/11 patients; in 2 of these it was necessary to reintroduce the basket after extraction of the stone, in order to eliminate small stone fragments and salivary sand; in 1 patient a preliminary balloon-catheter sialoplasty was performed prior to the procedure to dilatate a distal stenosis caused by chronic sialadenitis; in 3 patients it was necessary to make a small incision in the orifice to introduce the dilator. Removal of the sialolith was unsuccessful in 1/11 of the patients treated, as it proved impossible to capture the calculus, even after repeated attempts. 8/11 patients reported pain during the procedure and swelling in the gland region immediately after the procedure, which resolved spontaneously within 24-48 hours. 9/11 patients remained asymptomatic in the follow-up; only 1/11 patients experienced a recurrence of sialadenitis after a short time, with pus secretion, which resolved with antibiotic treatment. CONCLUSIONS: The interventional removal of sialoliths in the salivary glands is an effective alternative to the conventional treatment of obstructive diseases of the glandular ducts.

Adult↗

[Esophageal non-variceal hemorrhage: a clinical and epidemiological study].

Aim of this study was to evaluate the incidence of esophageal bleeding in a group of 3741 consecutive patients with acute non variceal upper gastrointestinal hemorrhage observed between January 1990 and January 1999 in the First Division of General Surgery--University of Verona. In 627 patients (16.8%) the source of bleeding was exclusively esophageal; and the most frequent causes of esophageal bleeding were reflux esopagitis (408 cases) and Mallory Weiss syndrome (185 cases). At emergency endoscopy, reflux esophagitis was actively bleeding in 83 cases (20.3%) and these patients presented a significantly higher frequency of cirrhosis and severe esophagitis; moreover a higher percentage of patients with bleeding esophagitis have had recent surgery and/or were hospitalized in an intensive care unit. No death directly related to the bleeding were observed, while ten patients deceased from other causes during the hospitalization. In more than half of the 185 patients affected by Mallory-Weiss syndrome a hiatal hernia was described and 69 (37.3%) were alcoholics with associated cirrhosis in 25 cases. In more than 70% of the cases the bleeding from a mucosal tear followed a vomit episode and the lesions were localized at the gastroesophageal junction. Endoscopic sclerotherapy was performed in 89 patients with active bleeding and hemostasis was initially obtained in all patients; rebleeding occurred in 6 patients (6.7%) who needed a further endoscopic treatment. No patients died during hospitalization. Other causes of esophageal bleeding observed were: Candida esophagitis (19 cases), esophageal malignancy (11 cases), benign polyps (2 cases), angiodysplasia (one case) and one case of aorto-esophageal fistula.

Adult↗

Two-year prospective evaluation of the factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: the key-role of age at diagnosis.

The aim of this study was to investigate the influence of pre-treatment variables on subsequent insulin requirement (IR) and partial remission (PR) in children with insulin-dependent diabetes mellitus (T1DM). Sixty-seven children with newly diagnosed T1DM, admitted to our Clinic during a 3-year recruitment period, were longitudinally evaluated for 2 yr. Patients were characterized by sex, age, parental education, duration of symptomatic history at diagnosis, admission duration, ketoacidosis or absence of ketoacidosis and residual beta-cell activity. More than 80% of the children experienced a PR, which lasted more than 12 months in 41.7% and at least 24 months in 16.4% of cases. The prevalence of PR at different ages after T1DM onset was significantly lower in children diagnosed while younger than 5 years than in those diagnosed after 5 years. The mean duration of the remission period was 11.7 +/- 8.9 months, irrespectively of sex, duration of the symptomatic period preceding T1DM diagnosis, parental education, blood pH and base excess, HbA1c concentration and admission duration. Beta-cell residual function evaluated after glucagons stimulation test (basal and 6 min C-peptide) was statistically different in PR patients and in those who experienced no remission. Age at diagnosis was the only pre-treatment factor which, on stepwise regression analysis, affected both PR duration and IR at the end of follow-up. To conclude, honeymoon frequency and duration are strictly conditioned by both residual beta-cell function and IR at T1DM onset. Since IR is higher in younger subjects, early onset of T1DM can be considered the factor with the most detrimental influence on honeymoon incidence. Other pre-treatment variables have no significant impact on PR.

Age Factors↗

ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds.

We present an RP-HPLC method for the determination of the octanol-water distribution coefficients at pH 7.4, as log values, for neutral and basic drugs, which combines ease of operation with high accuracy. The method is shown to work for a training set of 90 molecules comprised largely of drugs, and it was also applied to a test set of 10 proprietary compounds. This work expands the applicability of the method presented in our earlier report, for the determination of logP(oct) for neutral compounds (J. Med. Chem. 2000, 43, 2922-2928), and it offers the same general features but widens the scope. Generally, the method (i) is compound sparing (< or =1 mL of a 50-100 microg/mL solution needed), (ii) is insensitive to concentration and phase ratio effects observed in some shake-flask determinations, (iii) is amenable to rapid determinations (< or = 20 min on average), (iv) is insensitive to impurities, (v) possesses a wide lipophilicity range (>7 log units), and (vi) offers a good accuracy, (vii) an excellent reproducibility, (viii) and an excellent potential for automation. To the best of our knowledge, a similar performance, on a set of noncongeneric drugs, has not been previously reported. We refer to the value generated via this method as ElogD(oct).

1-Octanol↗

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.

Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15). Computational methodology for the rule-based Moriguchi Log P (MLogP) calculation is described. Turbidimetric solubility measurement is described and applied to known drugs. High throughput screening (HTS) leads tend to have higher MWT and Log P and lower turbidimetric solubility than leads in the pre-HTS era. In the development setting, solubility calculations focus on exact value prediction and are difficult because of polymorphism. Recent work on linear free energy relationships and Log P approaches are critically reviewed. Useful predictions are possible in closely related analog series when coupled with experimental thermodynamic solubility measurements.

Adsorption↗

CT features of malignant mucinous cystic tumors of the pancreas.

This study is aimed at evaluating which pre-operative findings at CT are prevailingly associated with histologically malignant appearance of mucinous cystic tumor (MCT) of the pancreas. The CT examinations of 52 female patients affected with pathologically proved MCT were retrospectively evaluated by two radiologists, blinded to the histopathological assessment of the biologic behavior (either benign or malignant). A multivariate logistic regression analysis was performed in order to identify the most important features associated with the malignant nature of MCT. Calcifications in the wall and/or in the septa, thick wall, and septations resulted in the most important features associated with malignancy. The simultaneous presence of all these radiological signs constitutes an almost "certain" marker of malignancy, being the risk equal to 0.95, whereas the simultaneous presence of at least two of them entails a risk of malignancy ranging from 0.56 to 0.74, according to the type of morphological features. On the other hand, the absence of the mentioned radiological features entails a negligible risk of malignancy (0.02). Mucinous cystic tumors characterized by multilocular macrocystic architecture, with thick wall and calcifications in the wall and/or the septa, present the highest risk of malignancy, and advocate prompt surgical intervention. When those signs are absent, the probability of malignancy is lower. In this case a non-operative management is possible.

Adult↗