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Biomedical subjects

G Milanese

Publications and source records attributed to G Milanese.

14 recordsLinked to original sources

Correlation between urodynamics and perineal ultrasound in female patients with urinary incontinence.

AIMS: We performed urodynamics and perineal ultrasound in female patients with urinary incontinence to assess morphology and function of the bladder base-urethra complex and of the detrusor muscle, and to find the correlation between these investigations in the diagnosis of (a) bladder neck and urethral hypermobility and (b) detrusor overactivity; we wanted to compare the tolerabililty of the urodynamic investigation and of the perineal ultrasound. METHODS: We considered 66 female patients referred to our outpatient clinic for urinary incontinence; we also studied 14 healthy control patients. After accurate case-history collection and physical examination, urodynamic investigation and perineal ultrasound were performed, with recording of parameters specific to both investigations. The statistical analysis was performed by ANOVA, Bonferroni post hoc test, and Spearman correlation test. The tolerability index between the diagnostic investigations performed was assessed by a 3-point scale suggested by the patient. RESULTS: In patients with stress incontinence the posterior urethro-vesical angle, the angle of urethral inclination, and the proximal pubo-urethral distance are significantly different under stress compared to the resting phase; in patients with urge incontinence, the detrusor wall is thicker and is accompanied by an increase in opening detrusor pressure and detrusor pressure at maximum flow; it is also accompanied by detrusor overactivity with increased urethral functional length. Increased urethral functional length is suggested on axial US images by alteration of its normal characteristic target-like appearance with four concentric rings of different echogenicity. In all cases the tolerability of perineal ultrasound has been higher than that of urodynamics. CONCLUSIONS: There is a good correlation between urodynamic and perineal ultrasound in the diagnosis of bladder neck and urethral hypermobility; perineal ultrasound can also be useful in the diagnosis of urge incontinence. Functional compressive urethral obstruction can be diagnosed on the basis of the ultrasound aspect of the urethral sphincter.

Adult↗

Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens.

PURPOSE: Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup. MATERIALS AND METHODS: A total of 48 patients with a mean age +/- SD of 58.2 +/- 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 +/- 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186). RESULTS: Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival. CONCLUSIONS: Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.

Adenocarcinoma, Clear Cell↗

Assessing effectiveness of home care for persons with AIDS: analysis of methodological problems.

The aim of this paper is to assess the methodological problems of an unsuccessful randomized controlled trial (RCT) conducted to evaluate the effectiveness, in terms of survival and quality of life, of the early offer of home care (HC) to persons with AIDS (PWA). The study carried out was an intention-to-treat RCT. Persons in the treatment group (TG) received the offer of HC at the moment of AIDS diagnosis; those in the control group (CG) received it six months from diagnosis. Many problems have hindered the progress of the study: particularly, the low compliance to the offer and the failure to enroll the required sample size have made the results unreliable. Analogous problems have been reported within other trials evaluating HC in different fields. The present study thoroughly evaluates the specific ethical and methodological problems encountered in designing and conducting a RCT on HC for PWA. We conclude that, before designing and conducting a RCT in this field, it is advisable to examine some main issues carefully, such as the acceptability of the offer of treatment, the expected compliance and the required size of the study population. If one or more of these elements prove to be problematic, the results of the trial risk being seriously compromised, and alternative approaches should be considered.

Acquired Immunodeficiency Syndrome↗

[Fragments of prostatic biopsy: characteristics, dimensions, and number].

Prostate needle biopsy can give important clinical information on tumor extension and grading, useful prognostic parameters for the therapeutic choice and prognostic definition. Currently about the 25% of positive biopsies for carcinoma contain only small foci of cancer that makes histopathological evaluation often the difficult and less reliable. We reviewed the literature about different methods to perform needle biopsies and methods to improve histologic yield of prostatic biopsies in order to obtain more histopathological information on the specimens to improve diagnostic accuracy on core biopsy. We report our initial experience using the preembedding methods proposed by Rogatsch. The best method to perform a prostate biopsy includes the use of using 18-gauges needles, single specimen identification and subsequent orientation of every bioptic fragment by inking its proximal end. We performed the preembedding technique of the fragments, proposed by Rogatsch et al., stretching the fragment between two nylon meshes enclosed in a tissue cassette in formalin. The full length of the biopsy is within the section plane. This technique partially modified in our preliminary experience with the employment of two sponges containing 10% buffered formalin placed in a tissue cassette (2.8 x 3.3 cm). This "sandwich" technique has furnished evident advantages for the pathologist, optimizing the visible area for section plane in comparison to that obtainable from free floating core biopsies. In conclusion, routinely application of the preembedding prostatic core biopsies could improve the accuracy of the histopathological examination and therefore provide more reliable data on tumor extension and grade.

Biopsy, Needle↗

[Intraprostatic spread of prostatic carcinoma: stereographic representation based on ultrasonography and biopsy findings].

The aim of this study is to identify and evaluate a scheme of graphic representation of the prostate, that allows the reconstruction of cancer diffusion based on ultrasound findings and on histological biopsy findings. A graphical representation of the prostate using transversal and longitudinal sections is represented by the US-operator, who write severy single performed biopsies (site, directions, and angle) and draws the US relieves. Biopsy specimens are separately prepared on a paper-support and marked at one extremity with china ink. The histopathological examination on every single specimen allows to identify the tumor extent, Gleason grading and the percentage occupied by the neoplasia. Were performed 50 transrectal echo-guided mapping biopsies. Comparing biopsy results with the pathological analysis on 13 whole-mount radical prostatectomy: pathological stage was predicted in 6 of 7 cases, Gleason grading was predicted in 85% of cases. In 5 cases in which the core biopsy histological analysis showed only atypical glands suspicious for cancer it has been possible to repeat new biopsies in the same site of the gland. Tumor was this time diagnosed in 3 of 5 cases (60%). The proposed approach can be useful to reduce variables linked to operator, technique, and single clinical situation, but it needs an employment on a higher number of cases and a verification on more surgical specimens. The scheme proposed has been of easy complication and immediate interpretation by clinicians and pathologists.

Aged↗

Heterogeneity of home care assistance needs of people with AIDS.

A multidisciplinary home care service for people with AIDS (PWAs) was started in Rome in September 1990. This paper describes the features of the home care service offered by the Associated Health Care Workers' Co-operative (OSA), an example of the integration of private and state systems. We detail the types and numbers of visits that PWAs have needed, and we explore the possible correlation between demographic and clinical variables and the care required. As of September 1994 service had been provided to 372 PWAs. During the 4-year period, 62,927 home care visits were made (an average of 4.3 visits/patient/week): 66% were made by psychologists, social workers and home helps, and 34% by health professionals. PWAs who, at the outset of their home care, suffered from AIDS-dementia complex (ADC), toxoplasmosis, wasting syndrome or cytomegalovirus retinitis required the highest number of visits. Psychologists, social workers and home care helps made more frequent visits than health professionals for all AIDS-defining conditions except retinitis (for which 63% of visits were for health care). Our study shows that careful assessment of patients receiving home care helps in planning visits and in organizing available resources. A controlled randomized multicentre study is under way with the aim of determining the effectiveness of home care in terms of survival, quality of life and care workload and related costs.

Acquired Immunodeficiency Syndrome↗

Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding.

The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF-treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.

Antigens, CD↗

Cystamine potently suppresses in vitro HIV replication in acutely and chronically infected human cells.

We have investigated the effects of cystamine on the replication of human immunodeficiency virus (HIV) in human lymphocytes and macrophages, the natural targets of HIV in vivo. Treatment of chronically infected macrophages with cystamine, at a concentration (500 microM) that did not show any cytotoxic or cytostatic effects, strongly decreased (> 80%) HIV-p24 antigen production and completely abolished the production of infectious viral particles. Cystamine does not affect viral transcription, translation or protein processing; indeed, all HIV proteins are present in a pattern similar to that of nontreated cells. Instead, cystamine interferes with the orderly assembly of HIV virions, as shown by electron microscopy analysis, that reveals only defective viral particles in treated cells. Moreover, suppression of HIV replication, due to the inhibition of proviral DNA formation was observed in acutely infected lymphocytes and macrophages pretreated with cystamine. These results show that cystamine potently suppresses HIV replication in human cells by contemporaneously blocking at least two independent steps of the viral life cycle, without affecting cell viability, suggesting that this compound may represent a new possibility towards the treatment of HIV-1 infection.

Antiviral Agents↗

Inhibition of the protease of human immunodeficiency virus blocks replication and infectivity of the virus in chronically infected macrophages.

Because of the importance of monocytes/macrophages (M/M) as an in vivo reservoir of human immunodeficiency virus (HIV), a study was done to investigate whether viral replication in chronically infected macrophages (HIV M/M) could be inhibited by various drugs, including U-75875, an inhibitor of HIV protease. HIV replication in M/M and in chronically infected T cells was dramatically decreased by U-75875, while other drugs, including zidovudine, interferon-alpha, and an antisense oligodeoxynucleotide against the rev gene, were effective antiviral agents only in de novo-infected cells. Virus titer in HIV M/M was reduced approximately 10(5)-fold by nontoxic concentrations of U-75875, while no effect on HIV DNA or virus antigen expression on cell membrane was achieved in M/M infected either chronically or de novo. Thus, U-75875 essentially worked against late stages of viral replication. These data support the use of protease inhibitors, alone or in combination, in the therapy of HIV-infected patients.

Antiviral Agents↗

Different pattern of activity of inhibitors of the human immunodeficiency virus in lymphocytes and monocyte/macrophages.

Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease.

Adenine↗

Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes.

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗

[Infectious diseases].

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Communicable Diseases↗