Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients. PATIENTS AND METHODS: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy. RESULTS: Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue. CONCLUSION: In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.     

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case–control study

Background  Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian.
Objectives  To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD).
Methods  Case–control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression.
Results  Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP.
Conclusions  There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.     

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years(mean±SEM) with chronic renal failure of varied aetiologywere randomized to receive either a conventional low proteindiet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphatediet (providing approximately 1000 mg phosphate plus an orallyadministered phosphate binder, minimum protein intake 0.8 g/kg/day;n=30) or to control (minimum protein intake 0.8 g/kg/day, nophosphate restriction; n=32). Patients were reviewed for a minimumof 6 months before randomization and were withdrawn from thestudy if plasma creatinine exceeded 900 µmol/1, plasmaphosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an averageof 19±3 months. Mean plasma creatinine rose from 398±33to 600±50 µmol/1. Dietary protein intake was estimatedat 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05in the low phosphate and 1.14±0.05 in the controls, phosphateintake was 815±43, 1000± 47, and 1315±57mg/day, respectively. Urinary urea excretion and protein catabolicrates were significantly reduced (p<0.01) only in those onprotein restriction, at 213±9 mmol/24 hours and 0.71g/kg/day, respectively. Phosphate excretion was significantlylower (p<0.05) in both the low protein group (17.9±0.8mmol/24 hours) and the low phosphate group (18.6±1.0mmol/24 hours) compared to controls. Changes in body weight,muscle mass and serum transferrin, albumin and immunoglobulinswere comparable between the groups. Mean blood pressure followingrandomization was 150/89±3/1 (low protein), 148/87±3/1(low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall ofcreatinine clearance (ml/min/ 1.73 m²/month), by rate of deteriorationderived from reciprocal plasma creatinine against time plots(1/mmol/year) and to assess individual patient's response totreatment by two phase linear regression (‘breakpoint’)analysis of reciprocal plasma creatinine/time plots. Progressionwas analysed only in patients seen for at least 3 months followingrandomization. The rate of fall of creatinine clearance was not significantlydifferent between the groups (ANOVA): 0.56±0.08 ml/min/1.73m2/month (low protein, n=28), 0.44±0.07 (low phosphate,n=23) and 0.69±0.11 (control, n=27). In 50 patients (18low protein, 16 low phosphate and 16 control) whose rate ofprogression could be calculated before and after randomization,there was a fall in rate of progression averaging 0.18 ml/min/1.73m2/month in those on low protein diet and those on low phosphatediet, but a rise of 0.08 in the controls. These differenceswere, however, not statistically significant. Similar resultswere obtained when the rates of deterioration were calculatedfrom plasma creatinine. Significant individual improvements(p<0.01) in rates of progression by ‘breakpoint’analysis occurred in 17 patients: six on low protein, sevenon low phosphate and in four controls. Sixty-one (72 per cent)of the patients examined by this method showed no significantchange in the rate of progression while seven patients had acceleratedprogression. There was no difference in the requirement formaintenance dialysis facilities between groups. No significant benefit of protein and phosphate restrictionwas therefore demonstrated.     

Kidney transplants in mice. An analysis of the immune status of mice bearing long-term, H-2 incompatible transplants

Kidney transplants between strains of mice which are incompatible at either the K or the D end of the H-2 complex usually function for prolonged periods supporting the lives of nephrectomized recipients. This occurs with no recipient treatment. With multiple H-2 and non-H-2 determined incompatibilities, transplants may be rejected but more slowly than skin grafts. In the strain combination studied most extensively in these experiments (B10.D2 to B6AF(1)) in which the incompatibility was confined to the K end of the H-2 region, about 70 percent of recipients survived for many weeks with normal blood urea nitrogen levels. Skin grafts between untreated members of these strains were rejected promptly (mean survival time of 13.5 +/- 1.1 days) as were kidney transplants to recipients of prior skin grafts. Donor strain skin grafts to recipients of kidney transplants after kidney transplantation enjoyed greatly prolonged survival whereas skin grafts from a third party (A.SW) were rejected normally. If kidney tissue was transferred in the form of free grafts without primary vascular union, it was rejected promptly leaving its recipient highly immunized. Cellular and humoral immunity to donor antigens declined over the first few weeks after transplantation, and the spleens of long-term recipients contained no “killer cells.” Recipient lymphoid cells could mount active graft versus host reactions to donor strain antigens on transfer to neonatal mice. Nevertheless, they were distinctly less able to respond specifically by the production of killer cells to donor strain antigens after sensitization in vitro. No evidence that this defect was associated with the presence of suppressor cells was forthcoming from several types of in vivo and in vitro tests.     

Polycystic Kidney Disease Re-evaluated: A Population-based Study

A genetic register of all known cases of autosomal dominantpolycystic kidney disease occurring in South and Mid-Wales hasbeen established. In a population of 2.1 million, 209 familieswith affected members were identified, 303 of whom are currentlyalive, 70 on renal replacement therapy. An additional 551 caseswould be predicted amongst family members at 50 per cent and25 per cent risk, giving an apparent prevalence of 1:2459 inthe general population. Five possible new mutations were seenwhere adults with phenotypic autosomal dominant polycystic kidneydisease had both parents alive, age > 55 years with no cystsvisible on ultrasound. The take-on rate for renal replacementtherapy increased during 1970–79 but has apparently reacheda plateau of 4.8 cases per million population per year overthe last 8 years, despite a rapidly increasing acceptance ofuraemic patients as a whole (72/10⁶/year in 1988–89).Considerably more patients with autosomal dominant polycystickidney disease aged over 50 years were started on treatmentin 1980–89 than in 1970–79, but the survival overallimproved with time. All cases of autosomal dominant polycystickidney disease reaching end-stage renal disease are now beingtreated, but the apparent clinical prevalence of this conditionin our region is less than half the supposed gene frequency,suggesting that undiagnosed cases have a benign prognosis.     

HDAC6 Deacetylates Ku70 and Regulates Ku70-Bax Binding in Neuroblastoma

Ku70 was first characterized as a nuclear factor that binds DNA double-strand breaks in nonhomolog end-joining DNA repair. However, recent studies have shown that Ku70 is also found in the cytoplasm and binds Bax, preventing Bax-induced cell death. We have shown that, in neuroblastoma cells, the binding between Ku70 and Bax depends on the acetylation status of Ku70, such that, when Ku70 is acetylated, Bax is released from Ku70, triggering cell death. Thus, to survive, in neuroblastoma cells, cytoplasmic Ku70 acetylation status is carefully regulated such that Ku70 is maintained in a deacetylated state, keeping Bax complexed with Ku70. We have shown that overexpression of CREB-binding protein (CBP), a known acetyltransferase that acetylates Ku70, releases Bax from Ku70, triggering apoptosis. Although we have shown that blocking deacetylase activity using non-type-specific inhibitors also triggers Ku70 acetylation and Bax-dependent cell death, the targets of these deacetylase inhibitors in neuroblastoma cells remain unknown. Here, we demonstrate that, in neuroblastoma cells, histone deacetylase 6 (HDAC6) binds Ku70 and Bax in the cytoplasm and that knocking down HDAC6 or using an HDAC6-specific inhibitor triggers Bax-dependent cell death. Our results show that HDAC6 regulates the interaction between Ku70 and Bax in neuroblastoma cells and may be a therapeutic target in this pediatric solid tumor.     

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...