Biomedical subjects
Publications and source records attributed to M Rizzo.
This paper describes 17 novel HLA-A alleles: A*0244, A*0251, A*0254, A*0309, A*1111, A*2432, A*2434, A*2504, A*2618, A*2905, A*2906, A*3106, A*3107, A*3207, A*6820, A*7407, and A*7408. Most substitutions are found in other alleles.
Twenty-five novel HLA-B alleles are described in this paper: B*0729, B*1309, B*1814, B*1815, B*2724, B*2725, B*3539, B*3926, B*4037, B*4040, B*4042, B*4043, B*4044, B*4204, B*440203, B*4428, B*4429, B*4430, B*4505, B*5308, B*5309, B*5510, B*5511, B*570102, and B*5709. Most of the variants are single nucleotide substitutions. Two involve variants at the Bw4/Bw6 epitope. Two alleles carry substitutions of conserved amino acids.
Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20-40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fisher's test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (chi(2) test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.
BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.
OBJECTIVE: To evaluate urinary symptoms, sexual dysfunction and quality of life in patients with benign prostatic hypertrophy (BPH) before and after open prostatectomy, using the International Prostate Symptom Score (IPSS), the International Continence Society (ICS)-"BPH" (ICS-male, ICS-sex and ICS-QoL) and International Index of Erectile Function (IIEF) questionnaires. PATIENTS AND METHODS: Sixty men with BPH (mean age 68 years) underwent a digital rectal examination, transurethral ultrasonography, measurement of total prostatic specific antigen serum level and uroflowmetry. Their urinary symptoms, sexual function and quality of life were fully evaluated using the IPSS, ICS-"BPH" and IIEF before and 6 months after suprapubic prostatectomy. The body mass index (BMI) was also calculated for each patient. Univariate analysis was used to examine the relationship between symptom scores and age, tobacco use, alcohol intake and BMI. RESULTS: In a univariate analysis, age was the most important prognostic factor for both urinary and sexual symptoms. Prostatectomy resulted in a significant improvement in obstructive (mean 9.68 to 3.38) and irritative symptom (6.70 to 3.06), and quality-of-life scores (3.41 to 1.34). ICS-male scores were both significantly decreased, the mean voiding score from 13.72 to 10.28 and the incontinence score from 10.43 to 7.81. There was also a significant decrease in the ICS-QoL symptom score (from 9.20 to 7.27). Comparative results between IIEF and ICS-sex showed no improvement in sexual scores after open surgery, but there was a significant increase in sexual desire and overall satisfaction (both P = 0.035). CONCLUSIONS: The combined use of the IPSS, ICS-"BPH" and IIEF allows an evaluation of the relationship between age, prostatic symptoms and sexual dysfunction. Age may be considered both a direct and indirect (BPH-related) prognostic factor for sexual activity. Suprapubic prostatectomy resolves obstructive symptoms, and maintains sexual desire, overall sexual satisfaction and an improvement in quality of life. However, irritative symptoms, erection, orgasm and sexual intercourse satisfaction are not significantly altered.
OBJECTIVE: To report a prospective, multicentre descriptive study designed to determine the prevalence of the diagnosis of prostatitis in male outpatients examined by urologists in Italy, and to further examine the diagnostic evaluation and treatment of patients identified with a clinical diagnosis of prostatitis. PATIENTS AND METHODS: Between July 2001 and October 2001, 70 urologists, representing a cross-section of urological centres in Italy, counted and recorded the overall total of men reported in the clinic and that of patients diagnosed with prostatitis over a 5-week period. Data on demographics, previous diagnoses, symptoms, physical examination, laboratory data and therapy instituted were collected. Patients with a diagnosis of prostatitis completed questionnaires on symptom frequency and severity, and quality of life. RESULTS: In all, 8503 patients were included in the primary outcome analysis; 1148 were identified with prostatitis (12.8%; mean age 47.1 years, range 16-83) with all age ranges equally represented, and 68% had had their first symptom within the last year. The most common presenting symptoms were severe, bothersome urinary frequency, obstructive voiding symptoms, perineal, suprapubic and penile pain or discomfort. The self-administered questionnaire confirmed that the most frequently reported and most severe symptoms at the time of evaluation were irritative voiding symptoms, perineal and suprapubic pain and discomfort. Over three-quarters of the patients were dissatisfied with their quality of life. While 98% of the patients had a digital rectal examination and expressed prostatic secretion was successfully recovered in 44%, < 3% of the patients had the traditional Meares-Stamey four-glass test. The most common treatment prescribed was drug therapy (not antibiotic). CONCLUSION: The prevalence of a clinical diagnosis of prostatitis in urology outpatient practice in Italy was 12.8%. The prevalence, diagnosis, evaluation and treatment of prostatitis reported in this prospective study was very similar to that reported in other retrospective series from other countries.
We describe a case of a monolateral duplex system and a ureterocele containing a gigantic stone in a 65-year-old woman who presented with pyelonephritis without any previous history of urinary tract infections or stone disease. Stone removal and double left ureteroneocystostomy with plastic widening of a narrowed obstructive side were performed. The ureteral stone measured 10.5 cm in greatest diameter, weighed 85 g and contained calcium oxalates and phosphates. Three months after surgery, radiology (intravenous urography and cystography) showed left unobstructed upper and lower urinary tracts and the absence of vesicoureteral reflux. Urine culture was negative 3, 6 and 9 months after surgery.
Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We describe the case of a patient with septic fever and a necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to drain the abscess content and to remove the necrotic tissue; mucormycosis was diagnosized by histological and culture tests and treated by intravenous amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly infused into the left common iliac artery, with progressive improvement, and treatment was continued until complete recovery. Therefore, the endoarterial infusion of liposomal amphotericin B was a safe and successful treatment of advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic administration probably is not sufficient to reach the whole infected area.
The present investigation was designed to develop an assay suitable for pharmacokinetic studies of new compounds, i.e. the novel 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one derivatives (2a and 2b), acting as non-competitive AMPA-receptor antagonists. A reversed-phase high-performance liquid chromatographic method has been developed to determine the time-course of plasma concentrations of derivatives 2a and 2b administered intraperitoneally to Sprague-Dawley rats. The separation of compounds studied and a N-methyl-2,3-benzodiazepin-4-one derivative as internal standard (I.S.) from plasma, were carried out by liquid-liquid extraction using diethyl ether. The samples were injected onto the analytical column (Partisil 10 ODS) eluted with acetonitrile/0.01 M acetate buffer (pH 5.3) at a flow-rate of 2 ml/min and detected at 240 nm. Compounds 2a, 2b and I.S. gave retention times of 8.5, 5.25 and 11.1 min, respectively. The selectivity of the method was satisfactory. The mean recovery from spiked rat plasma ranged from 86.7 to 91.6% for 2a, and from 85.1 to 87.0% for 2b. The procedures were validated with a good reproducibility and linear response from 0.0625 to 2 microg/ml, with a regression coefficient of 0.9932 for 2a and 0.9854 for 2b. The lower limit of quantification (LOQ) was taken as 15 ng/ml for the two compounds. 2a and 2b showed no signs of significant degradation in rat plasma during storage at -20 degrees C and following freeze/thaw cycles. Moreover, plasma levels of the tested compounds have been correlated with their anticonvulsant activity, determined in vivo in genetically epilepsy-prone rats. Due to its sensitivity, the method was suitable for application to pharmacokinetic study.
Concerns over penile size and a desire for a longer penis are common in the male population. The number of male patients seeking an andrological consultation for the problem of 'short penis' is increasing. We looked at the numbers of patients presenting to a University andrology clinic over a 2-y period and correlated their perceived penis size with the accepted norms. Sixty-seven patients were evaluated with a median age of 27 (range 16-55) complaining of 'short penis' and requesting surgical correction. Clinical history, including the IIEF-5 questionnaire and an accurate physical examination were obtained. Data concerning measures of penile length and circumference were recorded in both the flaccid and fully stretched states and compared to the normal reference range as previously described in the nomogram we recently published (Eur Urol 2001; 39: 183-186.). All patients were also asked to estimate the length of a normal sized penis.Fourty-four (65.7%) complained of a short penis only while flaccid, 22 patients (32.8%%) while both flaccid and erect, and only one patient (1.5%) was worried only by the erect length of the penis. Fifteen (22.4%) also complained about their penile circumference. Fifty-seven (85%) patients thought a 'normal' penile length should range from 10 to 17 cm (median value of 12 cm). Ten patients (15%) were not able to estimate 'normal' penile size. No patient was found to have a penile length under the 2.5 percentile according to our nomogram. Forty-two (62.7%) subjects recalled the problem starting in childhood, when they felt that their penis was smaller than their friends'. In 25 patients (37.3%) the problem started in the teenage years after seeing erotic images. Our data show that most men who seek penile lengthening surgery overestimate 'normal' penile length. In our series, none of the patients could be classified as having a severely short penis according to our nomogram and none had any anatomical penile abnormality. Most found the use of a nomgram to show them how they compared with other men helpful. We suggest that documentation of such a demonstration should be made for any man seeking an opinion on penile lengthening surgery.
Pseudomonas putida is a metabolically versatile saprophytic soil bacterium that has been certified as a biosafety host for the cloning of foreign genes. The bacterium also has considerable potential for biotechnological applications. Sequence analysis of the 6.18 Mb genome of strain KT2440 reveals diverse transport and metabolic systems. Although there is a high level of genome conservation with the pathogenic Pseudomonad Pseudomonas aeruginosa (85% of the predicted coding regions are shared), key virulence factors including exotoxin A and type III secretion systems are absent. Analysis of the genome gives insight into the non-pathogenic nature of P. putida and points to potential new applications in agriculture, biocatalysis, bioremediation and bioplastic production.
OBJECTIVES: From a series of glimpses, we perceive a seamless and richly detailed visual world. Cerebral damage, however, can destroy this illusion. In the case of Bálint's syndrome, the visual world is perceived erratically, as a series of single objects. The goal of this review is to explore a range of psychological and anatomical explanations for this striking visual disorder and to propose new directions for interpreting the findings in Bálint's syndrome and related cerebral disorders of visual processing. METHODS: Bálint's syndrome is reviewed in the light of current concepts and methodologies of vision research. RESULTS: The syndrome affects visual perception (causing simultanagnosia/visual disorientation) and visual control of eye and hand movement (causing ocular apraxia and optic ataxia). Although it has been generally construed as a biparietal syndrome causing an inability to see more than one object at a time, other lesions and mechanisms are also possible. Key syndrome components are dissociable and comprise a range of disturbances that overlap the hemineglect syndrome. Inouye's observations in similar cases, beginning in 1900, antedated Bálint's initial report. Because Bálint's syndrome is not common and is difficult to assess with standard clinical tools, the literature is dominated by case reports and confounded by case selection bias, non-uniform application of operational definitions, inadequate study of basic vision, poor lesion localisation, and failure to distinguish between deficits in the acute and chronic phases of recovery. CONCLUSIONS: Studies of Bálint's syndrome have provided unique evidence on neural substrates for attention, perception, and visuomotor control. Future studies should address possible underlying psychoanatomical mechanisms at "bottom up" and "top down" levels, and should specifically consider visual working memory and attention (including object based attention) as well as systems for identification of object structure and depth from binocular stereopsis, kinetic depth, motion parallax, eye movement signals, and other cues.
BACKGROUND AND AIM: The populations of the Mediterranean area have a low incidence of cardiovascular disease (CHD). The aims of this paper are: 1) to present demographic data of the population of Ustica, a small island in the southern part of the Tyrrhenian sea that has reduced communications with the mainland and a diet presumably rich in fish; and 2) to evaluate the distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in this population. METHODS AND RESULTS: We invited all of the free-living resident population aged more than 14 years (about 800 individuals) to participate in the study; 576 responded, for a participation rate of about 73%. The distribution of cardiovascular risk factors, plasma lipids, lipoproteins and dyslipidemias were evaluated in all of the subjects. More than 60% of the population was out of the normal weight range. Total and low-density lipoprotein cholesterol levels were respectively 207.4 +/- 46.7 and 141.7 +/- 42.4 mg/dL, and similar in males and females. Lipoprotein (a) (Lp[a]) levels presented the classical "skewed" distribution and, among the apolipoprotein(a) isoforms, there was a clear predominance of intermediate-sized kringle IV repeats. Overall, 43% of the subjects had a lipid disorder: the prevalence of hypercholesterolemia was 22.8% (3.2% with severe hypercholesterolemia terolemia > or = 300 mg/dL); low high-density lipoprotein cholesterol levels were found in 22.5%; the so-called lipid triad in 2.1%; and high Lp(a) levels in 6.2%. Large familial clusters were found for some lipid disorders. CONCLUSIONS: A large prevalence of body weight disturbances and high frequency of dyslipidemias are the main characteristics of this population. Ongoing data and future longitudinal studies will better clarify the relative influence of each parameter on CHD risk and total mortality.
BACKGROUND: This study investigated the sensitivity and specificity of a computer-automated telephone system to evaluate cognitive impairment in elderly callers to identify signs of early dementia. METHODS: The Clinical Dementia Rating Scale was used to assess 155 subjects aged 56 to 93 years (n = 74, 27, 42, and 12, with a Clinical Dementia Rating Scale score of 0, 0.5, 1, and 2, respectively). These subjects performed a battery of tests administered by an interactive voice response system using standard Touch-Tone telephones. Seventy-four collateral informants also completed an interactive voice response version of the Symptoms of Dementia Screener. RESULTS: Sixteen cognitively impaired subjects were unable to complete the telephone call. Performances on 6 of 8 tasks were significantly influenced by Clinical Dementia Rating Scale status. The mean (SD) call length was 12 minutes 27 seconds (2 minutes 32 seconds). A subsample (n = 116) was analyzed using machine-learning methods, producing a scoring algorithm that combined performances across 4 tasks. Results indicated a potential sensitivity of 82.0% and specificity of 85.5%. The scoring model generalized to a validation subsample (n = 39), producing 85.0% sensitivity and 78.9% specificity. The kappa agreement between predicted and actual group membership was 0.64 (P<.001). Of the 16 subjects unable to complete the call, 11 provided sufficient information to permit us to classify them as impaired. Standard scoring of the interactive voice response-administered Symptoms of Dementia Screener (completed by informants) produced a screening sensitivity of 63.5% and 100% specificity. A lower criterion found a 90.4% sensitivity, without lowering specificity. CONCLUSIONS: Computer-automated telephone screening for early dementia using either informant or direct assessment is feasible. Such systems could provide wide-scale, cost-effective screening, education, and referral services to patients and caregivers.
BACKGROUND: Once a person identifies a visual object, the ability to detect a second object is impaired for the next few hundred milliseconds. This attentional blink is reported to increase in subjects with neglect due to acute right hemisphere lesions. METHOD: To examine neural substrates of the attentional blink, the authors examined the performance of 13 subjects with chronic focal brain lesions visualized by MRI and nine control subjects without neurologic impairments on a rapid serial visual presentation task that used letters as targets. RESULTS: Attentional blink length in the lesion group was more than twice that of controls (p < 0.05). The magnitude of the attentional blink deficit was greatest when the second target appeared 200 ms after the first target, recovering close to baseline by 1,200 ms. Abnormal attentional blink occurred (even in the absence of neglect) with lesions in the occipitotemporal areas (associated with "object" vision) and the prefrontal cortices (thought to mediate visual working memory). CONCLUSIONS: Attentional blink length and attentional blink magnitude measure different components of the attentional blink process. Abnormal attentional blink can occur with different chronic focal brain lesions in a network of structures for vision and attention, and it has no special status in hemispatial neglect. Abnormal attentional blink may help explain difficulties on rapid, visually demanding cognitive tasks such as reading and automobile driving and may explain performance deficits in brain damaged patients with nonspatial disorders of visual processing.
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PURPOSE: Elevated plasma concentrations of low-density lipoproteins (LDL) increase risk for coronary heart disease. However, lipoprotein profiles rich in small, dense LDL particles confer greater risk than those that mainly consist of large, buoyant LDL. This may be due, in part, to the greater oxidative susceptibility of small, dense LDL. In the current studies, we tested whether differences in the oxidative behavior of buoyant and dense LDL arise from differences in their immediate metabolic precursors, intermediate-density lipoproteins. SUBJECTS AND METHODS: We compared the properties of intermediate-density lipoproteins and buoyant and dense LDL subfractions in 9 subjects with the large, buoyant LDL phenotype versus 6 with the small, dense LDL phenotype. Oxidative susceptibility was evaluated based on conjugated diene formation and parinaric acid oxidation induced by copper. Antioxidants (ubiquinol-10 and alpha-tocopherol) were measured by high-performance liquid chromatography. RESULTS: Oxidative susceptibility was increased and antioxidant concentrations were decreased with increasing lipoprotein density (intermediate intermediate-density lipoproteins to buoyant LDL to dense LDL). Intermediate-density lipoproteins from subjects with the small, dense LDL phenotype had a greater oxidative susceptibility (by the parinaric acid test) and lower antioxidant concentrations than corresponding particles from subjects with the large, buoyant LDL phenotype. CONCLUSIONS: Differences in oxidative susceptibility between large, buoyant and small, dense LDL particles are apparent in their lipoprotein precursors. These results suggest that lipoprotein oxidative susceptibility may be metabolically programmed and that intermediate-density lipoproteins may contribute to the increased risk associated with the small, dense LDL phenotype.
Preparation for reaches to visual targets depends on sensorimotor transformations (SMT) between target and limb coordinate systems. To examine neural substrates for SMT, we studied 19 individuals with focal lesions of the visual association cortices and white matter and 11 control subjects without brain lesions. SMT were assessed by measuring accuracy of reaches to remembered locations of visually presented targets. Results showed abnormally large SMT errors in all individuals with inferior parietal lobule (IPL) lesions and some subjects with lesions of the temporo-occipital regions and in occipital area 19. Types of abnormal errors (direction or distance) varied between subjects with similar lesions, e.g. IPL. Patterns of abnormality included dissociations of distance and direction errors and of constant and variable errors. These findings are compatible with the hypothesis of different systems for guiding distance and direction of reaches distributed among structures in superior and inferior visual association cortex.