Characterization of biochemical recurrence after radical prostatectomy

BACKGROUND: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). METHODS: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. CONCLUSIONS: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.     

Trauma Exposure and Posttraumatic Stress Disorder in Adolescents: A National Survey in Switzerland

There are a limited number of epidemiological studies that have focused on trauma exposure and prevalence of posttraumatic stress disorder (PTSD) in representative general population samples of adolescents, especially outside of the United States. We therefore aimed to assess the lifetime prevalence of traumatic events (TEs) and current prevalence of PTSD, and to examine demographic risk factors for TEs and PTSD in a representative sample of adolescents. Data were collected by a school survey among a sample of 6,787 9th‐grade students in Switzerland. Roughly 56% of the adolescents (females 56.6%; males 55.7%) reported having experienced at least 1 TE. Non‐Swiss nationality (OR = 1.80), not living with both biological parents (OR = 1.64), and lower parental education (OR = 1.18) were associated with a higher risk of trauma exposure. The current prevalence of PTSD according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM‐IV‐TR; American Psychiatric Association, 2000) criteria was 4.2% (females 6.2%; males 2.4%). Female gender (OR = 2.70), not living with both biological parents (OR = 1.47), lower parental education (OR = 1.51), and exposure to multiple TEs (OR = 9.56) were significant risk factors for PTSD. Results suggest considerably high rates of TEs and PTSD among adolescents. Intervention efforts must be intensified to reduce trauma exposure and treat PTSD.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

From recipe to research: introducing undergraduate students to the nature of science using a hybrid practical course centred on drug discovery for neglected diseases

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Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Peripheral arterial disease: identification and implications

Peripheral arterial disease (PAD) is most commonly a manifestation of systemic atherosclerosis in which the arterial lumen of the lower extremities becomes progressively occluded by atherosclerotic plaque. Patients with PAD are at triple the risk of all-cause mortality and at more than 6 times the risk of death from coronary heart disease as those without the disease, yet PAD is probably the most underdiagnosed and least aggressively managed atherosclerotic disease. In the diagnosis of PAD, a detailed history and physical examination are extremely important, although limited by a lack of consistent sensitivity and specificity. Other office-based noninvasive tests, including the ankle-brachial index, can be easily performed to confirm the diagnosis and help stratify the risk. The ankle-brachial index correlates well with disease severity and functional symptoms and can also be used to assess disease progression and to predict cardiovascular and cerebrovascular mortality. Once diagnosed, risk factor modification, symptomatic relief, and secondary prevention strategies with antiplatelet agents form the core of medical management of PAD.     

A statistical analysis of murine stem cell suicide techniques

The clinical application of soft agar cloning techniques for granulocyte-macrophage stem cells (CFU-C) has resulted in a number of contradictory reports that may in part be due to an inadequate data base. Growth of murine CFU-C is more reproducible and less variable than that of human CFU-C. We utilized in vivo hydroxyurea suicide of murine marrow CFU-C to address the question of how many experiments are needed to detect a specific difference with a p of less than 0.05. In 66 experiments the mean marrow CFU-C hydroxyurea kill was 23.3%; 6-9 separate experiments were necessary to detaect differences of 25%-30%. In order to be sure that a 25%-30% difference is not present, 15-21 experiments were required. Using a Dec-20 computer, 1000 samples of sample size 3, 4, or 10 were drawn from the 66 experiments; it was found that with 3 experiments and a true value of 23%, the actually observed value was below 10%, 17% of the time, and was over 40% in 10% of the samplings. In a smaller number of experiments similar results were obtained analyzing 3HTdR suicide of pluripotent stem cells and CFU- C. These data could provide a base from which to judge the validity of studies utilizing the CFU-C technique.