Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an antioxidant effect in a mouse model of type 2 diabetes

Cell therapy has been extensively investigated in heart disease but less so in the kidney. We considered whether cell therapy also might be useful in diabetic kidney disease. Cognizant of the likely need for autologous cell therapy in humans, we sought to assess the efficacy of donor cells derived from both healthy and diabetic animals. Eight-week-old db/db mice were randomized to receive a single intravenous injection of PBS or 0.5 × 10(6) early-outgrowth cells (EOCs) from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion. Untreated db/db mice developed mesangial matrix expansion and tubular epithelial cell apoptosis in association with increased reactive oxygen species (ROS) and overexpression of thioredoxin interacting protein (TxnIP). Without affecting blood glucose or blood pressure, EOCs not only attenuated mesangial and peritubular matrix expansion, as well as tubular apoptosis, but also diminished ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating kidney injury and oxidative stress. The similarly beneficial effects of cells from healthy and diabetic donors highlight the potential of autologous cell therapy in the related clinical setting.     

Patterns and predictors of symptom incongruence in older couples coping with prostate cancer

Purpose

Prostate cancer survivors (PCSs) may experience persistent symptoms following treatment. If PCSs and spouses differ in their perceptions of symptoms, that incongruence may cause mismanagement of symptoms and reduced relationship quality. The purpose of this study was to examine symptom incongruence and identify the PCS and spouse characteristics associated with symptom incongruence in older couples coping with prostate cancer.

Methods

Participants in the study were older PCSs (>60 years) and their spouses (N?=?59 couples). Symptom incongruence was determined by comparing patient and spouse independent ratings of the severity of his cancer-related symptoms. Predictor variables included PCS age, time since diagnosis, PCS comorbidity, PCS and spouse depressive symptoms, and spouse caregiving strain.

Results

PCS and spouse ratings of his symptom severity and the amount of incongruence over his symptoms varied significantly across couples. Overall, couples rated a moderate level of PCS symptom severity, but PCSs and their spouses significantly differed in their perceptions of PCS symptom severity with spouses rating severity higher (t?=??2.66, df?=?51, p?<?0.01). PCS younger age and high spouse caregiver strain accounted for 29 % of incongruence in perceptions of PCS symptom severity.

Conclusions

This study is among the first to show that PCSs and spouses may perceive cancer-related persistent symptoms differently. Among this older sample, younger PCS age and spouse caregiver strain were associated with incongruence in symptoms perceptions in couples. These and other factors may inform future interventions aimed at preserving relationship quality in older couples who have experienced prostate cancer.     

Cryotherapy for docetaxel-induced hand and nail toxicity: randomised control trial

Purpose

This study investigated the efficacy and safety of cryotherapy, in the form of frozen gel gloves, in relation to docetaxel-induced hand and fingernail toxicities.

Patients and methods

After piloting with 21 patients, a consecutive series sample of patients (n?=?53) prescribed docetaxel every 3 weeks, for a minimum of three cycles, was enrolled in this randomised control trial. Participants acted as their own control, with the frozen gel glove worn on one randomised hand for 15 min prior to infusion, for the duration of the infusion, and for 15 min of after completion of treatment. Hand and nail toxicities were evaluated by two blinded assessors according to CTCAE.v4 criteria. To assess the potential for cross-infection of multi-use gloves, microbial culture and sensitivity swabs were taken of each glove at every tenth use.

Results

Of the 53 participants enrolled in the main study, 21 provided evaluable data. There was a 60 % withdrawal rate due to patient discomfort with the intervention. The mean incidence and severity of toxicities in all evaluable cycles in control and intervention hands respectively were erythroderma grade 1 (5/5 %), nail discolouration grade 1 (81/67 %), nail loss grade 1 (19/19 %) and nail ridging grade 1 (57/57 %). No significant differences were determined between hand conditions in terms of time to event, nor in terms of toxicity in gloved and non-gloved hands.

Conclusion

While cryotherapy in the form of frozen gloves for the cutaneous toxicities associated with docetaxel is safe, its limited efficacy, patient discomfort and some logistical issues preclude its use in our clinical setting.     

Satellite in vitro fertilization: The Oregon experience

Objective: This study was designed to compare the results of preliminary evaluation, ovarian hyperstimulation, and monitoring of patients at a distant in vitro fertilization satellite center with those treated at the main campus of the program.Study design: Fifty-four patients completing oocyte retrieval cycles at the Eugene satellite Oregon Health Sciences University in vitro fertilization program for the period Jan. 1, 1991, through Dec. 31, 1993, were compared with 222 patients at the main campus for age, peak estradiol level, number of oocytes, retrieved, number of embryos, clinical pregnancy rate, and pregnancy outcome.Results: There were no statistically significant differences between the Eugene in vitro fertilization satellite center and the main campus for any of the factors analyzed with the exception of clinical pregnancy rate. The clinical pregnancy rate per cycle at the Eugene satellite center was 39% while the Portland main campus rate was 23% (p = 0.027), presumably because of a larger number of couples with severe male factor infertility at the central site.Conclusion: A distant in vitro fertilization satellite program was highly successful in the Oregon experience. In addition to greater convenience to the patients, the program was highly comparable to main campus program in measured parameters of ovarian hyperstimulation, oocyte retrieval, number of embryos, and pregnancy rate.     

Tuberculosis of the knee

Summary Ninety-eight cases of tuberculosis of the knee (85 adults and 13 children), treated by one or other of the authors, were reviewed. 70% of the patients presented an advanced stage of destructive disease, but 30% were seen at the stage of synovitis. A proven diagnosis was obtained in 88 out of 98 cases. In the majority, treatment was standardised with 6 to 12 months of chemotherapy and plaster immobilisation in order to prevent or correct a deformity. Arthrodesis was only undertaken for disabling deformity after conservative management (16 cases). Response to chemotherapy was favourable in 78 followed-up patients. Five relapses occurred between the 12th and 24th month. The functional results ranged from full normal recovery to spontaneous fusion or arthrodesis. The results were related to the stage of the disease at the time when treatment was started.

---

Résumé Etude rétrospective de 98 cas de tuberculose du genou (85 adultes et 13 enfants) toutes traitées personnellement par un des auteurs; sur le plan diagnostique, 70% des patients se présentaient à un stade de destruction articulaire assez avancée mais 30% cependant furent vus pour la lère fois au stade de synovite. Le diagnostic scientifique fut obtenu dans 88 cas sur 98. Dans tous les cas, sauf 6, le traitement a été standardisé: chimiothérapie de 6 à 12 mois suivant les époques, immobilisation plâtrée pour prévenir ou corriger les déformations et arthrodèse en cas de déformation finale persistante (16 cas). Les résultats ont été bons en ce qui concerne la réponse à la chimiothérapie: 78 réponses favorables chez 78 patients suivis. Il y a eu 5 rechutes du 12ème au 24ème mois. Du point de vue orthopédique, les résultats finaux — depuis la récupération d'une flexion normale jusqu'à la fusion spontanée et la déformation résiduelle obligeant à l'arthrodèse — ont été essentiellement dépendants du degré de destruction articulaire au début du traitement. Teutes les arthrodèses ont été pratiquées chez des patients porteurs de grosses lésions anatomiques au ler examen. Enfin la synovectomie est rejetée par les auteurs qui la considèrent comme toujours incomplète et en règle inutile.

     

Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer

PURPOSE: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). METHODS AND MATERIALS: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. RESULTS: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p=0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p=0.0008). CONCLUSIONS: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.