Fluorescence in situ hybridization analysis of c-myc amplification in stage T3N0M0 prostate cancer in Japanese patients

OBJECTIVE: Genetic aberration such as the amplification of c-myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c-myc gene), related to the progression and survival in advanced (Stage C) prostate cancer. MATERIALS AND METHODS: We used dual-probe fluorescence in situ hybridization with a centromere-specific probe for chromosome 8 (8cen), and with a region-specific probe for c-myc (8q24) to evaluate genetic changes in tumor samples from 50 patients who had undergone radical retropubic prostatectomy from 1986 to 2001. RESULTS: We classified the 8cen and c-myc copy numbers as normal, gain and amplification. The carcinoma foci with extra copies of c-myc, which was defined in 35 cases (70%), were divided into two groups: (a) a simple gain of the whole chromosome 8 (no increase in the c-myc copy number relative to the chromosome 8 centromere), which was identified in 15 cases (30%); and (b) a substantial amplification of c-myc (additional increases [AI] in the c-myc copy number relative to the chromosome 8 centromere), which was detected in 20 cases (40%). AI-c-myc was strongly associated with higher histopathological grades and Gleason's scores (P = 0.0330, 0.0190, respectively). Patients with the AI-c-myc had earlier disease progression (P = 0.0029) and earlier cancer death (P = 0.0087) than did patients with normal patterns. CONCLUSION: Identification of an AI-c-myc may serve as a potential marker of prostate cancer progression.     

Ca2+Mg3+-ATPase activity in erythrocyte membranes in hypercalciuric nephrolithiasic patients

SUMMARY: Ca²⁺Mg²⁺ATPase is an enzyme involved in calcium transport across biological membranes. In order to determine its possible role in the pathogenesis of calcium nephrolithiasis, we assessed Ca²⁺Mg²⁺-ATPase activity in erythrocyte membranes from 18 hypercalciuric (HC) nephrolithiasic patients (nine with absorptive hypercalciuria (AHC), nine with renal hypercalciuria (RHC)) and eight normocalciuric healthy controls (C). Participants took no medication for at least 3 months before the study and remained on a diet containing approximately 25 mmol of calcium per day for 14 days. Pump activity was measured in calmodulin-free red blood cell membranes and expressed in umol of phosphate released per mg of membrane protein per h. There were statistically significant differences in pump activity between groups (1.43±0.07; 1.93±0.1; 1.65±0.06; C, AHC, RHC, respectively, P < 0.005 (three groups) and P < 0.02 AHC versus RHC. Enzyme activity was positively correlated with 24-h urinary calcium excretion (r = 0.64, P < 0.01) in HC patients; no such relationship was found in C. In conclusion, erythrocyte membrane Ca²⁺Mg²⁺ATPase activity is increased in HC. Differences in enzyme activity between AHC and RHC may reflect different degrees of a single generalized epithelial calcium transport disturbance.     

Transcutaneous Pco2 in adults

Using a transcutaneous Pco₂ (PtcCO₂) electrode, arterial Pco₂ (Paco₂) was compared with PtcCO₂in eight adults (seven patients, one normal subject) over a wide range of values of PaCO₂(2.4 to 7.87 kPa). At an electrode temperature of 43°C, PtcCO₂=1.25 Paco₂kPa (95% confidence limits: 0.60 kPa). Change in PtcCO₂accurately reflected change in Paco₂.     

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2–12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5–17) with an initial dose of 600 mg/m²/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5–5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m²/12 h (range 415–970), which maintained mean C₀-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2–5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.     

Gastric carcinoma developing in chronic gastric ulcer in the rat treated with N-methyl-N1-nitro-N-nitrosoguanidine

The purpose of this experiment was to determine if chronic gastric ulcer in the rat is prediposed to tumor formation when exposed to a known gastric carcinogen. N-methyl-N¹-nitro-N-nitrosoguanidine (NG). Rats were subjected to a standard ulcer-producing operation. Treatment with oral NG (as drinking water) was continued for at least 40 weeks. Appropriate control groups underwent sham operation and/or were fed with tap water. The experiment terminated at 52 weeks. The results showed that significantly more tumors were found at the edge of a chronic ulcer or at the site of previous mucosal injury in the rats which had the ulcer-producing operation and fed with NG than controls (P < 0.005). However, the number of tumors per rat stomach was the same when the rats were treated with NG whether an ulcer-producing operation or a sham operation was carried out. Furthermore, $\text{18}\text{52}$ rats in the group with ulcer-producing operation and NG had chronic ulcers without tumors. It is concluded that, in the rat, the presence of a chronic gastric ulcer is more likely to localize the development of a tumor to the ulcer or to the site of previous injury, but does not increase the overall incidence of gastric tumors.     

Comparison of the haemodynamic actions of desflurane/N2O and isoflurane/N2O anaesthesia in vascular surgical patients

Background: The purpose of this study was to compare heart rate and arterial blood pressure response to desflurane/N₂O vs isoflurane/N₂O anaesthesia in a randomised clinical trial performed in patients before vascular surgery.
Methods: To evaluate associated changes in the autonomic nervous system with maintenance of anaesthesia, we used power spectral analysis (PSA) of heart rate and blood pressure and measured plasma catecholamine concentrations. Twenty-five patients whose trachea had been intubated after propofol induction were given either desflurane or isoflurane at 1 and 1.5 MAC in N₂O (60%) in a random manner.
Results: At an anaesthetic depth of up to 1.5 MAC, arterial blood pressure, indices of sympathetic activity derived from PSA, decreased with both anaesthetics, while heart rate and plasma catecholamine concentrations did not significantly change. Plasma renin activity significantly increased at 1.5 MAC anaesthesia in both groups.
Conclusions: We conclude that sympathetic hyperactivity previously reported during desflurane anaesthesia in healthy volunteers is not frequent in clinical practice in elderly vascular surgical patients under desflurane/N₂O anaesthesia, since it occurs at an anaesthetic depth which cannot be reached in these patients because of the lowering arterial blood pressure effects of desflurane, which are similar to those of isoflurane.     

Variation in numbers of CD4+CD25highFOXP3+ T cells with normal immuno-regulatory properties in long-term graft outcome

Chronic rejection (CR) is a major cause of long-term graft loss that would be avoided by the induction of tolerance. We previously showed that renal transplant patients with CR have lower numbers of peripheral CD4(+)CD25(high) T cells than operationally tolerant patients, patients with stable graft function and healthy volunteers (HV). We explored here the profile of CD4(+)CD25(high) blood T cells in these patients focusing on their expression of the regulatory T cells (Treg) gene Forkhead Box P3 (FOXP3) and their suppressive function. We show that CR is associated with a decreased number of CD4(+)CD25(high)FOXP3(+)T cells with normal regulatory profile, whereas graft acceptance is associated with CD4(+)CD25(high)FOXP3(+)T cell numbers similar to HVs. These data suggest that Treg numbers, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of renal transplants.     

FDG-PET/CT in the staging of local/regional metastases in breast cancer

Breast cancer is the commonest female malignancy in the Western world and the most reliable predictor for survival is axillary lymph node metastases. Conventional staging techniques employed in breast cancer include mammography, ultrasonography, isotope bone scanning, sentinel lymph node biopsy, axillary lymph node dissection and magnetic resonance imaging. More recently FDG-PET and FDG-PET/CT have been used to complement the above methods. This review assesses the role of FDG-PET/CT in axillary staging in patients with primary breast cancer.A PubMed search was conducted and all articles containing relevant or new information were included. Relevant studies examined identified that FDG-PET/CT has a sensitivity of 60% and a specificity of 97% in detecting lymphatic metastasis.Although positive axillary FDG-PET/CT is a good predictor of axillary disease and correlates well with SLNB, the relatively poor sensitivity (60%) must be considered for treatment planning.     

Stress/aging: endocrine profiles/reproductive dysfunction in men

Extensive investigations have been carried out on the biology/physiology of stress [13, 18, 20, 25, 35, 48, 49, 53, 55], pathophysiology of aging [41], sexual dysfunction [7, 27] and adrenal insufficiency [4, 31].