Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: possible induction of benign prostatic hyperplasia

Rhesus monkeys were used to investigate the role of androgenic steroids and estradiol in the induction of hyperplastic changes in stromal and glandular prostate tissues. Adult male rhesus monkeys were procured from the wild and, after routine quarantine procedures, were randomly divided into 5 groups of 5 animals each. Gluteus maximus muscles were injected with 2.5 mg of androstenedione (Group II), 2.5 mg of dihydrotestosterone (DHT) or 0.25 mg of estradiol (Group II), 2.5 mg androstanediol (Diol; Group IV), or Diol in combination with 0.25 mg of estradiol (Group V). Group I consisted of untreated controls. Animals were injected with steroids 3 times a week for 2 years. Treatment with androstenedione (Group II) resulted in stromal hyperplasia in the caudal lobe and an increase in epithelial cell height in all zones except in the central zone of the caudal lobe. In monkeys treated with DHT and estradiol (Group III), stromal hyperplasia in both lobes, a decrease in tubular size, and degranulation and vacuolation of epithelial cells were noticed. Injection of Diol alone (Group IV) or in combination with estradiol (Group V) resulted in a widening of stroma in the central and peripheral zones of cranial and caudal lobes, whereas the tubular size decreased. Diol also induced epithelial cell hypercellularity in the central and peripheral zones of the caudal lobe and in the peripheral zone of the cranial lobe. Prostate-specific antigen levels in Group IV animals gradually increased from 6 months of treatment and were maximal after 18 months of injections. Serum estradiol levels increased to detectable levels in all groups except Group IV. Serum testosterone levels decreased to very low or undetectable levels in all groups, whereas prostate-specific acid phosphatase increased in all treated groups. Prolactin levels were elevated in all treated groups except in animals injected with androstenedione. These results indicate that repeated long-term injections of androstenedione or DHT and estradiol induced stromal hyperplasia, which may be an estrogen-related effect. Androstanediol-induced hypercellularity and stratification of glandular epithelium is comparable to human prostatic intraepithelial neoplasia. These results also suggest that the rhesus monkey is a suitable animal model for experimental induction of prostate diseases.     

Assessment of patellar maltracking using combined static and dynamic MRI

Between January 1995 and Jul 1997, 474 patients with anterior knee pain resistant to conservative treatment were referred for MR of the knee. The MR examination consisted of routine sequences with an additional patellofemoral dynamic examination using a technique that has been developed at this institution. The dynamic study examines both knees simultaneously, with the patient supine and the quadriceps loaded. No gating or restraint apparatus is needed. Patellar subluxation or tilt was present in 188(40 %) of cases, bilateral in 104 and unilateral in 84 cases (right 39, left 45). It was classified as mild in 51 %, moderate in 39 % and severe in 10 %. Subluxation was more prevalent in females than males (42 % vs. 37 %) and this was most obvious in the severe group where 68 % were female. In 90 knees selected at random, four measurements of patellofemoral morphology were obtained using reconstructed images from a volume gradient echo sequence. These measurements were correlated with the degree of subluxation or tilt. A tibial tubercle distance greater than 20 mm, a femoral sulcus angle greater than 150 degrees, sulcus depth less than 4 mm were specific for subluxation but no measurement proved to be sufficiently sensitive to preclude a tracking study. MRI can be used to define more precisely the anatomy of the extensor mechanism and its relationship to the femur and tibia, in both a static and dynamic setting. In this way, patients with anterior knee pain can be classified more accurately and the outcomes of treatment more reliably assessed. Received: 17 September 1999; Revised: 31 January 2000; Accepted: 4 February 2000     

Post-traumatic cervical dystonia: a distinct entity?

BACKGROUND/OBJECTIVE: The incidence of head/neck trauma preceding cervical dystonia (CD) has been reported to be 5-21%. There are few reports comparing the clinical characteristics of patients with and without a history of injury. Our aim was to compare the clinical characteristics of idiopathic CD (CD-I) to those with onset precipitated by trauma (CD-T). METHODS: We evaluated 114 consecutive patients with CD over a 9-month period. All patients were interviewed using a detailed questionnaire and had a neurological examination. Their clinical charts were also reviewed. RESULTS: Fourteen patients (12%) had mild head/neck injury within a year preceding the onset of CD. Between the two groups (CD-I and CD-T), the gender distribution (F:M of 3:2), family history of movement disorders (32% vs. 29%), the prevalence of gestes antagonistes (65% vs. 64%), and response to botulinum toxin were similar. There were non-specific trends, including an earlier age of onset (mean ages 43.3 vs. 37.6), higher prevalence of neck pain (86% vs. 100%), head tremor (67% vs. 79%), and dystonia in other body parts (23% vs. 36%) in CD-T. CONCLUSIONS: CD-I and CD-T are clinically similar. Trauma may be a triggering factor in CD but this was only supported by non-significant trends in its earlier age of onset.     

Anti-inflammatory activity of Indian black tea (Sikkim variety).

In this study, the anti-inflammatory (in reference to the cardinal signs of inflammation) and other related pharmacological activities of the hot water extract of black tea (Camellia sinensis, Sikkim variety) were evaluated along with certain standard drugs. The extract showed significant inhibitory activity against carrageenin, histamine, serotonin and prostaglandin-induced pedal inflammation. The extract inhibited exudative inflammation. The tea extract also inhibited cotton pellet-induced granuloma formation and adjuvant-induced polyarthritis. Black tea extract showed significant inhibition against glucose oxidase-mediated inflammation. The present observations establish the efficacy of this particular variety of black tea, both in the exudative and proliferative forms and as well in the chronic phase of inflammation.     

Structural,optical, and magnetic properties of Ag+, Mn+ and Ar+ ions implanted ZnO thin films: effect of implantation dose and stopping energy

Herein, we systematically studied the effect of various excitation processes on the structural, optical, and magnetic properties of ZnO films implanted with 80 keV Ar⁺, 110 keV Mn⁺, and 190 keV Ag⁺ ions. Four different doses of 1 × 10¹³, 1 × 10¹⁴, 1 × 10¹⁵, and 2 × 10¹⁶ ions per cm² were used for implantation. It was observed that the structural, optical, and magnetic properties of the implanted samples were dominantly affected at the highest dose of 2 × 10¹⁶ ions per cm². For lower doses, insignificant changes in these properties were observed. A comparison of various processes involved in the implantation process shows that both the electronic excitation and nuclear excitation processes are responsible for the changes in the structural, optical, and magnetic properties of the implanted ZnO films.

Dominant changes in structural, optical, and magnetic properties were observed at the highest dose of implanted ions with larger ionic radii which is due to the large number of produced defects in the host.     

Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review

Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies.

Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI.

Results Included patients (n?=?325 for everolimus and n?=?127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with?<6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup.

Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors.

Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.