Prostate-specific antigen doubling time before onset of chemotherapy as a predictor of survival for hormone-refractory prostate cancer patients.

BACKGROUND: We evaluated the possible use of prostate-specific antigen doubling time (PSA-DT) before chemotherapy initiation as a surrogate marker of survival in hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Data from 250 consecutive metastatic HRPC patients treated with chemotherapy between February 2000 and November 2006 were retrospectively analysed. At least three PSA assays were required within 3 months before chemotherapy. PSA-DT was calculated as ln 2 divided by the slope of the log PSA line, and the difference between two log PSA levels was divided by the time interval. The primary endpoint was overall survival (OS). Survival rates according to PSA-DT were stratified on chemotherapy regimen. Multivariate Cox regression analysis was performed to isolate the impact of PSA-DT on OS, controlling for associate prognostic covariates. RESULTS: Patients received docetaxel- (82%) or mitoxantrone-based chemotherapy. The median PSA-DT was 45 days (range 4.7-1108 days). There were 174 deaths (70%). The median survival was 16.5 months (95% confidence interval [CI] = 12.5-20.5) and 26.4 months (95% CI = 20.3-32.4) for patients with a PSA-DT < 45 and > or =45 days, respectively. In the multivariate setting, the adjusted hazard ratio (HR) was 1.39 (95% CI = 1.03-1.89; P = 0.04), stratified by chemotherapy regimen. CONCLUSION: A short PSA-DT before onset of chemotherapy in HRPC patients was associated with an increased risk of death. This could be useful as a stratification parameter in trials with new drugs in a metastatic setting.     

Observations questioning a protective role for breast-feeding in severe rotavirus diarrhea

To investigate whether breast-feeding protects children against rotavirus diarrhea (RVD), we compared rates of breast-feeding by age and enteric pathogens among 2,276 children with diarrhea 0-4 years of age who attended a diarrhea hospital in Bangladesh. Infants 0-5 months were less likely to be breast-fed than children 6-11 months of age suggesting that some protection against diarrhea with all agents was associated with early breast-feeding. In every age group studied, breast-feeding was more common among children with RVD than among children with non-RVD whereas it was less common among children with cholera and shigellosis. Twenty percent of breast milks consumed by infants less than 1 year of age had high levels of neutralizing activity (greater than or equal to 320) to the Wa strain of rotavirus but this activity did not appear to be protective since the 30 infants with RVD consumed milk which had titers that did not differ significantly from those consumed by 44 infants with diarrhea of other cause. Despite the prolonged breast-feeding which is common in Bangladesh, the mean age of hospitalization with RVD is approximately the same as in countries where the duration of breast-feeding is quite short. None of these 3 independent observations support a protective role for breast-feeding against rotavirus diarrhea after the first months of life.     

Cephalic tetanus as a result of rooster pecking: an unusual case

In this paper, a case of cephalic tetanus caused by rooster pecking to the face is presented. Cephalic tetanus is a rare type of tetanus defined by trismus and paralysis of 1 or more cranial nerves. On admission to hospital the patient had facial palsy and trismus. With proper medical management she recovered without any relapse.     

Diurnal variation of intraocular pressure and its correlation with retinal nerve fiber analysis in Turkish patients with exfoliation syndrome

Purpose The purpose was to evaluate the diurnal variation (DV) of intraocular pressure (IOP) in patients with exfoliation syndrome (XS), to measure retinal nerve fiber layer (RNFL) thickness by using scanning laser polarimetry, and to compare these measurements with those of normal subjects. Methods Forty-five subjects with XS and 40 healthy, age/sex matched subjects were recruited into the study. A detailed ophthalmologic examination was performed. IOP measurements were obtained at 08:00 am, 12:00 pm, 03:00 pm, and 06:00 pm. The XS group was further divided into DV ≥5 mmHg and DV<5 mmHg groups and also according to the existence of IOP fluctuation. The IOP measurements and RNFL thickness measurements were compared between the groups. Results The mean IOP value was found to be highest in the morning both in the XS and control groups. IOP showed a gradual decrease from 8.00 am to 6.00 pm in the control group, whereas a second peak at 03:00 pm was observed in the XS group. There was a fluctuation in 53.3% of the XS group, while none of the healthy subjects showed fluctuation. Superior and inferior ratios were statistically lower in XS patients than those in control subjects (p<0.05). Moreover, in patients with XS showing a DV ≥5 mmHg and/or a fluctuation, the superior ratio, inferior ratio, the number, superior average and superior integral were significantly different (all p values <0.05) from those of control subjects. Conclusions As the XS patients with high diurnal IOP variation and fluctuating pattern of IOP had lower RNFL thickness measurements, it is crucial to follow up these patients by performing scanning laser polarimetry in order to discover any possible glaucomatous damage at an earlier stage than with the use of conventional visual field analysis.     

Granulocytic sarcoma of the heart: extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone

We present a case of granulocytic sarcoma (GS) of the heart. A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation. Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML. The involvement of the heart with GS is very rare and this is the first case of extramedullary disease in the heart after allogeneic transplantation. Here we present the case history and related literature has been reviewed.     

Prostate cancer: update

The study of mitotic transduction of the signal showed that overexpression of pAkt and reduction in pERK expression would be associated a biological relapse. For tumors T1-3 N0M0 at the high risk of local relapse after prostatectomy, an immediate radiotherapy compared with a differed radiotherapy (at the time of PSA relapse), showed a significant reduction in the rate of local relapse and an ameliorated progression free survival. The effectiveness of the docetaxel was confirmed in two phase III randomized clinical trials : TAX-327 with 3 arms compared docetaxel every 21 days, docetaxel every 7 days and mitoxantrone. All arms were prednisone-based. An increase in overall survival, PSA progression free survival, PSA response rate and a pain reduction were highlighted in the docetaxel arm every 21 days. Docetaxel obtained at the end of this study the marketing authorization in this indication and became the treatment of reference. The SWOG 99-16 study compared the docetaxel estramustine association with the same arm of reference, mitoxantrone and prednisone, with similar results. The addition of estramustine to the docetaxel seems to improve the PSA response rate and progression free survival, but with a greater embolic toxicity. The addition of an antiangiogenic agent, the thalidomide, to docetaxel, improves progression free survival and overall survival. PSA responses were observed with an inhibitor of the proteasome, the bortezomib, in monotherapy, contrary to the imatinib which in monotherapy didn't have any effectiveness. Studies in association with docetaxel are ongoing. Some biological responses were observed with a vaccine anti MUC-1 and must be confirmed on a greater series of patients. The docetaxel impact on localized disease is actually evaluated.     

Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans. METHODS: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints. RESULTS: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice. CONCLUSIONS: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.