Should patients with a pre-operative prostatespecific antigen greater than 15ng/ml be offered radical prostatectomy?

Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml. Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed. Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106). Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative lymph node frozen section.     

Transmission of hepatitis A in hamburg, germany, 1998-1999--A prospective population based study

To study the pattern of transmission of HAV in a large urban community a prospective cohort study was conducted in Hamburg between 1 January 1998 and 31 December 1999. Four hundred and eleven patients were classified as hepatitis A cases comprising 144 foreign and 267 German persons. Univariate analyses were carried out to examine differences between socio-demographic, clinical and behavioural characteristics. To determine independent predictors for HAV infection a multiple logistic-regression model was used. The principal risk factor was travel to areas where hepatitis A is endemic, with 32.6% (n = 134/411) of all documented cases of hepatitis A. Foreign patients who had acquired the infection abroad, mostly children, accounted for the majority of these cases. Of all 411 cases, 42 (10.2%) were associated with parenteral drug, followed by day-care or school contact (8.3%; n = 34). Outbreaks contributed to 11.4% of cases (n = 47), but only 7.1% (n = 29) were household contacts. The low incidence rate among exposed persons in the households of those infected was similar in the groups of foreign and German nationals (17/384 = 4.4% and 12/231 = 5.2%, respectively), which may demonstrate a good hygienic level in general. Our findings suggest that preventive measures such as the improvement of hygienic conditions in a defined general population may contribute to a reduced incidence of hepatitis A. Nevertheless, because hygienic standards may change with time, this policy should be supplemented by targeted vaccination of groups at risk.     

Relationship between the chest radiograph, regional lung function studies, exercise tolerance, and clinical condition in cystic fibrosis

This study evaluated the accuracy of the interpretation of the chest film in delineating localised abnormalities of ventilation and perfusion, as well as the overall severity of airways obstruction, exercise tolerance, and clinical condition in children with cystic fibrosis. Radiographic findings in various regions of the chest film were compared with the functional values obtained with regional lung function tests which evaluated the arrival and disappearance of boluses of radioactive nitrogen given by inhalation and infusion. While the more severely affected areas on the chest radiograph were found to correlate with similar regions on the lung function tests, as did overall scores, errors occurred in some cases if the x-ray film alone was used as a judge of regional physiological derangement. In addition the degree of airways obstruction, the exercise tolerance on a cycle ergometer, and clinical grading, each correlated significantly with the radiographic score. We conclude that the chest radiograph is a good indicator of the overall severity of the lung disease and that it correlates well with exercise tolerance and clinical condition in cystic fibrosis.     

SARS-CoV-2 B.1.1.7 Variant Infection in Malayan Tigers,Virginia, USA

We report infection of 3 Malayan tigers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) variant at a zoologic park in Virginia, USA. All tigers exhibited respiratory signs consistent with SARS-CoV-2 infection. These findings show that tigers are susceptible to infection with the SARS-CoV-2 B.1.1.7 variant.     

Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy

Purpose

This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy.

Methods

Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogenization, and assessed in vitro on human fibroblasts from MPS I patients and in vivo on MPS I mice for IDUA production and gene expression.

Results

The physicochemical results showed that the presence of DSPE-PEG in the formulations led to smaller and more stable droplets even when submitted to dilution in simulated nasal medium (SNM). In vitro assays showed that pIDUA/NE-PEG complexes were internalized by cells, and led to a 5% significant increase in IDUA activity, besides promoting a two-fold increase in IDUA expression. The NA of pIDUA/NE-PEG complexes to MPS I mice demonstrated the ability to reach the brain, promoting increased IDUA activity and expression in this tissue, as well as in kidney and spleen tissues after treatment. An increase in serum IL-6 was observed after treatment, although with no signs of tissue inflammatory infiltrate according to histopathology and CD68 assessments.

Conclusions

These findings demonstrated that pIDUA/NE-PEG complexes could efficiently increase IDUA activity in vitro and in vivo after NA, and represent a potential treatment for the neurological impairment present in MPS I patients.

     

Comparative responses of three rat strains (DA/Han,Sprague-Dawley and Wistar) to treatment with environmental estrogens

The rat uterotrophic assay is a widely used screening test for the detection of estrogenic, endocrine-disrupting chemicals. Although much attention has been paid to identifying protocol variables and reproducibility between laboratories the question whether toxicodynamic and toxicokinetic variations of different strains may affect their sensitivity to estrogenic stimuli has been rarely addressed. We have compared the estrogenic activity of the environmental chemicals genistein (GEN), bisphenol A (BPA) and p-tert-octylphenol (OCT) in DA/Han (DA), Sprague-Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were treated per os for 3 days with different doses of these weakly estrogenic compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine wet weight, thickness of the uterine epithelium, uterine gene expression of clusterin (CLU), and thickness of the vaginal epithelium were examined as parameters for estrogenic potency of the test compounds in the three strains of rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in the three strains, and allowed us to rank them as GEN being more potent than OCT, and BPA being the weakest estrogen. This was confirmed by analysis of other biological endpoints, despite some differences in the magnitude of their response among strains and to distinct compounds. For instance, the uterus wet weight response to EE treatment indicated lower sensitivity of SD rats than that of DA and WIS rats, but this was not observed for responses of the uterine or vaginal epithelium. Moreover, blood concentrations were assessed at the time of killing and related to biological responses: plasma levels of total and unconjugated BPA and GEN depended upon the dose administered and varied to some extent within treatment groups and among the three rat strains. However, there was no good correlation in the three strains between individual compound concentrations analysed 24 h after the last dose and the uterotrophic wet weights. Summarising our results, we conclude that the sensitivity of various biological endpoints can differ slightly between strains of rats. On the other hand, our data demonstrate that the choice of the rat strain does not lead to pronounced differences in the evaluation of estrogenic activities of chemicals, especially when different biological endpoints are included in the analysis.     

Regulation of gene expression by 8-prenylnaringenin in uterus and liver of Wistar rats

The potential estrogenic activity of 8-prenylnaringenin has been investigated using several in vitro test systems. 8-Prenylnaringenin is a natural secondary product of the female blossoms of hops. The aim of the present study was to characterize 8-prenylnaringenin for its estrogenic effects in vivo. A three day uterotrophic assay was carried out on ovariectomized young female rats. A single dose of 8-prenylnaringenin (10 mg/day/kg body mass) was administered subcutaneously. 17beta-Estradiol (0.03 mg/day/kg body mass; subcutaneous administration) was used as a positive control. Uterine wet weight, endometrial and vaginal epithelial height were determined by histological methods. Gene expression in uterus and in liver was assessed using realtime RT-PCR. Both estradiol and 8-prenylnaringenin significantly stimulated uterine wet weight accompanied by a proliferative response. The three day treatment resulted in a statistically significant increase of the uterine epithelial height as well as of the vaginal epithelial height, the latter being the more sensitive parameter. In the uterus of ovariectomized animals estrogen receptor-alpha and clusterin gene expression were down regulated following treatment with estradiol, whereas expression of complement C3 was up-regulated. In response to treatment with 8-prenylnaringenin the same gene expression pattern was detectable, but less pronounced. The levels of estrogen receptor-alpha mRNA in rat liver were very low and therefore could not be quantitatively assessed. Like in the uterine tissue, estradiol down regulated clusterin expression. The response to 8-prenylnaringenin was weaker but still significant. Conversely, 8-prenylnaringenin was found to be more potent than estradiol in inducing expression of IGFBP-1. In summary, the multiparametric assessment of the estrogenic activity of 8-prenylnaringenin provides overwhelming evidence that 8-prenylnaringenin has largely to be regarded as a pure estrogen agonist and is therefore a questionable candidate molecule for hormone replacement therapy.