Associations of HIV testing and late diagnosis at a Japanese university hospital.

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Predictive factors for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus.

BACKGROUND: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia. METHODS: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection. RESULTS: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia. CONCLUSIONS: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.

Questionnaire-based analysis of atovaquone-proguanil compared with mefloquine in the chemoprophylaxis of malaria in non-immune Japanese travelers.

Malaria is one of the most common and serious infectious diseases in the tropics and subtropics. For high-risk travelers to endemic regions, malaria chemoprophylaxis is recommended. Internationally, atovaquone-proguanil (A/P), mefloquine (MEF), or doxycycline (DOX) are the prescribed malaria chemoprophylactic drugs. However, A/P and DOX are not approved in Japan. Therefore, the data on A/P for malaria chemoprophylaxis in Japanese travelers are not clear. We analyzed questionnaire survey data obtained in Hibiya Clinic to assess the safety and tolerability of A/P and compare them with those of MEF for non-immune Japanese travelers. A/P was given to 278 travelers and MEF to 38 travelers. The mean duration of each prophylaxis is for 20.0 ± 9.6 and 59.0 ± 15.9 days, respectively. Nine travelers discontinued prophylaxis: 5 in the A/P prescribed group (A/P group) and 4 in the MEF prescribed group (MEF group), and the rate of discontinuation was significantly less in the A/P group. The frequency of adverse events was significantly less in the A/P group than in the MEF group [52 cases (18.8 %) vs. 14 cases (36.8 %), respectively]. In particular, the frequency of psychoneurotic adverse events was significantly less in the A/P group. These results suggest that A/P is better tolerated and has fewer adverse events than MEF in non-immune Japanese travelers.

Clinical characteristics and risk factors for mortality in patients with bacteremia caused by Pseudomonas aeruginosa.

OBJECTIVE: The mortality rates for bacteremia due to Pseudomonas aeruginosa remain high. In our hospital, we performed retrospective analyses to determine risk factors for mortality among patients with bacteremia caused by P. aeruginosa. MATERIALS AND METHODS: This retrospective cohort study was conducted among adult patients with bacteremia due to P. aeruginosa at Jikei University Hospital. We analyzed factors, such as age, gender, underlying disease, initial antimicrobial treatment, and primary site of infection to determine which of these were predictive of mortality in patients with P. aeruginosa bacteremia. RESULTS: One hundred and thirty-four patients with P. aeruginosa bacteremia were identified between April 2003 and March 2010. The 30-day mortality rate among all patients with P. aeruginosa bacteremia was 20.9%. The most common underlying disease was leukemia (20.9%), and the most common primary site of infection was the urinary tract (24.6%). Seventy-one patients (65.7%) were treated with an appropriate initial antimicrobial regimen for P. aeruginosa bacteremia. However, these patients had similar 30-day mortality to that observed in patients not administered appropriate antibiotics. This study revealed that risk factors for the 30-day mortality were thrombocytopenia and polymicrobial P. aeruginosa bacteremia (p<0.01). CONCLUSION: Thrombocytopenia and polymicrobial bacteremia were associated with a greater incidence of 30-day mortality among patients with P. aeruginosa bacteremia. On the other hand, age, underlying disease, and inappropriate initial empirical antimicrobial treatment did not affect mortality.

Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck.

OBJECTIVE: We evaluated the clinicopathological findings and short- and long-term outcomes of prostate cancer (PCa) patients with bladder neck invasion who underwent cystoprostatectomy. PATIENTS AND METHODS: Between 1989 and 2005, we performed 17 cystoprostatectomies for PCa patients having bladder neck invasion without distant visceral or distant lymph node metastasis. Of the 17 patients, 11 were treated with neoadjuvant hormone therapy and all patients were treated with adjuvant hormone therapy immediately after surgery. RESULTS: All 7 patients in whom pelvic lymph node swelling was identified by preoperative imaging studies had pathological lymph node metastasis. Of the 10 patients judged as cN0 preoperatively, 7 (70.0%) had lymph node metastasis. Although local recurrence was found in 2 (11.8%) patients, no additional urinary diversion or inconvenient urinary symptoms due to PCa progression were observed in any patients. The 5-year prostate-specific antigen recurrence-free survival rate was 62.2%. Cause-specific survival at 5 years after surgery was 87.1%. The 5-year cause-specific survival rate of node-positive patients was 92.3%. CONCLUSION: Cystoprostatectomy followed by immediate hormone therapy may be a feasible treatment option to achieve excellent local control for patients with previously untreated PCa, even in the presence of pelvic lymph node metastasis.

Prospective evaluation of selection criteria for active surveillance in Japanese patients with stage T1cN0M0 prostate cancer.

OBJECTIVE: Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program. METHODS: Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) 2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of '%PSADT > 2y' was expected to be >80%. RESULTS: One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT > 2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired. CONCLUSIONS: The primary endpoint, '%PSADT > 2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

Bone marrow-derived cells mobilized by granulocyte-colony stimulating factor facilitate vascular regeneration in mouse kidney after ischemia/reperfusion injury.

Bone marrow-derived cells (BMDC) play crucial roles in tissue regeneration. Granulocyte-colony stimulating factor (G-CSF) mobilizes BMDC and may facilitate the repair of kidney tissues after ischemia/reperfusion (I/R) injury. The tissue protective action of resveratrol, an antioxidant, might modify the regenerating potential of BMDC in I/R renal injury. This study examined whether G-CSF and/or resveratrol affect the recruitment of BMDC into vascular endothelial cells and renal tubular cells and the kidney function after I/R injury. I/R renal injury was induced in female mice that had been lethally irradiated and transplanted with male bone marrow cells. The mice were given saline, resveratrol or G-CSF, daily for 7 days. Non-irradiated and non-bone-marrow-transplanted female mice, which underwent the same kidney injury, were included as control. White blood cell (WBC) count and serum creatinine were monitored. Immunohistologic evaluation for renal tubular cells (cytokeratin) and endothelial cells (factor VIII-related antigen), and fluorescence in situ hybridization for mouse Y chromosome were performed. Although WBC was significantly higher in the G-CSF group, there was no significant difference in creatinine levels among all groups. Factor VIII-related antigen-positive cells with a Y-chromosome signal were identified in the capillary wall between renal tubuli and most frequently seen in the G-CSF group (p < 0.0001). Resveratrol did not affect kidney recovery in this model. No cytokeratin-positive renal tubular cells having a Y-chromosome signal were identified. In conclusion, BMDC are recruited into endothelial cell in I/R renal injury without apparent renal tubular cell regeneration, and G-CSF facilitates the endothelial cell regeneration.

[Clinical features of lung cancer HIV-infected patients].

Since HIV infection and opportunistic infections began to be treated by highly active antiretroviral therapy (HAART), the incidence of cancers, especially lung cancer increased. The clinical course of lung cancer in HIV infected patients is more aggressive, and little is known about its features or management. We retrospectively evaluated 6 cases of lung cancer with HIV infected patients in Tokyo Metropolitan Komagome Hospital. All patients were male and current smokers. Adenocarcinoma, squamous cell carcinoma and small cell carcinoma were observed in 3, 2 and 1, respectively. There were 2 cases each of clinical Stage I, IIIB, and IV were each 2 cases. The range of the CD4 cell count was 52-432/microL. HIV infection was confirmed concurrently with the diagnosis of lung cancer or complications in 5 of 6 patients. Some cases treated for both lung cancer and HIV, had a relatively good clinical course. We suggest that cancer treatment concurrently with HAART may be useful for similar cases. Further experience and study are necessary.

Association of BCL10 germ line polymorphisms on chromosome 1p with advanced stage testicular germ cell tumor patients.

The association between four BCL10 single nucleotide polymorphisms at codons 5, 8, 162, and intron 1 and the susceptibility or progression for germ cell tumors (GCTs) was investigated in 73 testicular GCT patients and 72 controls. GCT patients with metastatic disease were more likely to have a variant type allele of the polymorphisms at codon 5 (age-adjusted odds ratio (aOR)=6.25; 95% CI=1.09-35.83; P=0.040) and codon 8 (aOR=4.63; 95% CI=1.35-15.93; P=0.015) than those with the localized disease. Therefore, BCL10 polymorphisms at codons 5 and 8 may play a role in the progression to advanced stage GCTs.

Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis.

PURPOSE: We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). MATERIALS AND METHODS: Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. RESULTS: Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). CONCLUSIONS: In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.

A long-term survival case of small cell lung cancer in an HIV-infected patient.

We report a case of small cell lung cancer in a patient with human immunodeficiency virus (HIV) infection. The patient was a 51-year-old man diagnosed 8 years previously as seropositive for HIV, who was admitted to our hospital for re-evaluation of antiretroviral medications due to multidrug resistance. Chest radiograph revealed an abnormal hilar shadow subsequently confirmed to be small cell lung cancer. He received chemotherapy concurrently with highly active antiretroviral therapy (HAART), and lived for 14 months after the diagnosis. The prognosis of lung cancer in HIV-seropositive patients is very poor, and adverse effects of chemotherapy occur more frequently than in other patients. However, the simultaneous antiretroviral agents and combination chemotherapy was successful. Such treatment may be effective despite an otherwise poor prognosis, including HIV infection.

Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection.

PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

CYP3A5 gene polymorphism and risk of prostate cancer in a Japanese population.

The CYP3A5 gene (CYP3A5) encodes the cytochrome P450 3A5, which catalyzes the 6beta-hydroxylation of testosterone. We explored association between the CYP3A5 A6986G polymorphism and a risk of prostate cancer in 260 prostate cancer patients, 199 BPH patients and 212 male controls. The CYP3A5 gene polymorphism did not influence significantly a risk of developing of prostate cancer in general. However, compared with males with the GG genotype, those with the AA genotype had a 0.23-fold decreased risk of developing low-grade prostate cancer (P=0.023), and a 0.31-fold decreased risk of developing localized (stages A-C) prostate cancer (P=0.044). The CYP3A5 A6986G polymorphism may be specifically associated with a decreased risk of low-grade or early stage prostate cancer.

Association of a genetic polymorphism of the E-cadherin gene with prostate cancer in a Japanese population.

The E-cadherin gene has been identified as having a physiological role in cellular attachment, and is hypothesized to participate in carcinogenesis. A polymorphism (an A to C substitution) in the 5'-untranslated region has a direct effect on E-cadherin gene transcriptional regulation. We explored the association between E-cadherin gene polymorphism and the risk of prostate cancer in a Japanese population. The subjects consisted of 236 patients with prostate cancer, 209 benign prostatic hyperplasia (BPH) patients and 139 male controls. A marginally significant difference was found between prostate cancer patients and male controls (P = 0.053). No significant difference was observed between prostate cancer and BPH patients. When patients with prostate cancer were divided into two groups, stage A+B and stage C+D, a significant difference was observed between progressive cancer patients (stage C+D) and male controls (odds ratio = 1.93, P = 0.016). It is possible that the presence of one A allele resulted in an increased risk of cancer progression.

[Two cases of urothelial cancer responsive to high-dose-intensity methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy].

We report two cases of metastatic urothelial cancer treated with high-dose-intensity (HD) methotrexate vinblastine, doxorubicin and cisplatin (MVAC). After HD-MVAC, the size of primary and lymph node tumors decreased by 57-67% as compared with the standard M-VAC therapy. By shortening the dose interval, HD-MVAC may increase the anti-tumor effect without increasing side effects.

A retrospective study of the treatment of locally advanced prostate cancer by six institutions in eastern and north-eastern Japan.

OBJECTIVE: To investigate patients with locally advanced prostate cancer treated at six academic institutions in eastern and north-eastern Japan from 1988 to 2000, to facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer. PATIENTS AND METHODS: The study included 391 eligible patients with locally advanced prostate cancer who were treated by radical prostatectomy (RP), radiotherapy and/or primary hormone therapy. Disease-specific survival rates for these patients were assessed in relation to their clinicopathological characteristics and the types of treatment they received. The Mann-Whitney U-test, Kruskal-Wallis, chi-square and log-rank test were used for statistical analysis, as appropriate. RESULTS: In all, 128 patient with lower prostate-specific antigen levels (P = 0.023) and/or better performance status (P = 0.001) had RP. Neoadjuvant hormone therapy before RP was the treatment in 68 (53%) of these 128 patients; 66 (52%) received immediate adjuvant hormone therapy. Of 87 patients treated with radiotherapy, 75 (86%) had external beam radiotherapy (EBRT) as the primary treatment with no brachytherapy, and 12 (14%) had brachytherapy as the primary method. Neoadjuvant hormone therapy was given to 56 of the 87 patients (64%); 48 (55%) received immediate adjuvant hormone therapy. Of the 176 patients treated with primary hormone therapy alone, combined androgen blockade and surgical or medical castration was the treatment in 76 (43%) and 85 (48%), respectively. Disease-specific survival rates at 5 years for patients treated with RP, EBRT and primary hormone therapy were 90%, 98%, and 89%, respectively. CONCLUSION: The treatments provided by the participating institutions did not differ significantly from those set out in European and American guidelines, and short-term disease-specific survival rates for each treatment did not differ significantly from those of historical controls. Further investigation may facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer.

CA repeat polymorphism in the insulin-like growth factor-I gene is associated with increased risk of prostate cancer and benign prostatic hyperplasia.

Insulin-like growth factor-I (IGF-I) plays an important role in prostate growth, hyperplasia, and carcinogenesis. Circulating IGF-I levels may be modulated by a genetic cytosine-adenine (CA) repeat polymorphism in the promoter region of IGF-I. The association of the polymorphism with the risk of prostate cancer and benign prostatic hyperplasia (BPH) was explored in 303 patients with prostate cancer, 219 patients with BPH and 262 controls. The number of CA repeats ranged from 15 to 22 in case and control subjects. The 19-CA-repeat allele (19-allele) was more frequently observed in both the prostate cancer and BPH patients compared with the controls (prostate cancer versus control: P<0.001; BPH versus control: P=0.001). Compared with non-carriers of the 19-allele, men homo-zygous for the 19-allele had a significantly increased risk of prostate cancer [age-adjusted odds ratio (aOR) = 3.36, 95% confidence intervals (CI) = 1.30-8.67, P=0.012] or BPH (aOR = 3.53, 95% CI = 1.32-9.46, P=0.012), and those heterozygous for the 19-allele also had an intermediate increased risk of prostate cancer (aOR = 1.78, 95% CI = 1.25-2.53, P=0.001) or BPH (aOR = 1.66, 95% CI = 1.14-2.43, P=0.009). A gene dosage effect for the aORs was found with an increasing number for the 19-allele (P<0.001 in prostate cancer and P=0.001 in BPH). No significant association was found between the presence of the 19-allele and the tumor stage and grade at the time of diagnosis. In conclusion, the 19-allele of IGF-I appears to increase the risk of prostate cancer and BPH with a gene dosage effect in the Japanese population.

Association of the cyclin D1 gene G870A polymorphism with susceptibility to sporadic renal cell carcinoma.

PURPOSE: Cyclin D1 (CCND1) mRNA is alternatively spliced to produce 2 transcripts (transcript-a and transcript-b), which may be modulated by a G870A single nucleotide polymorphism at the conserved splice donor site of exon 4. Previous studies have suggested a significant association between the CCND1 genotype and the development of various cancers. We explored the possible association between this polymorphism and the onset or disease statue of sporadic renal cell carcinoma (RCC). MATERIALS AND METHODS: The CCND1 G870A genotype was determined in 191 RCC cases and in 400 controls by polymerase chain reaction restriction length polymorphism analysis. RESULTS: Subjects with the AA genotype were at 1.70-fold significant higher risk for RCC than those with the GG genotype (age and sex adjusted OR 1.70, 95% 95% CI 1.03 to 2.82, p = 0.039). In addition, the A allele had a gene dose effect in increasing the risk of RCC (adjusted OR 1.30, 95% CI 1.01 to 1.67, p = 0.045). For tumor stage no significant difference in genotype frequency was found (p = 0.646). CONCLUSIONS: These data suggest that the CCND1 variant A allele may be a genetic susceptibility factor with a recessive or gene dose effect for the onset of sporadic RCC. More extensive and larger studies are required to clarify whether the CCND1 genotype is more specifically involved in the onset of a histological subset of RCC or RCC at a younger age.

Influence of pretransplant dialysis modality on the change of lymphocyte subset populations and acute rejection rates after renal transplantation.

BACKGROUND: The influence of dialysis modality on the acute rejection (AR) rate after renal transplantation is controversial. We investigated whether the pretransplant dialysis modality correlated with the lymphocyte subset populations and the incidence of AR after renal transplantation. METHODS: Thirty-eight first living renal transplant recipients, consisting of 22 patients on pretransplant hemodialysis (HD) and 16 patients on pretransplant peritoneal dialysis (PD), were studied. Peripheral blood samples were taken on days -1 through 28 after transplantation, and the lymphocyte fractions were exposed to the monoclonal antibodies anti-CD3, CD19, CD4, CD8 and CD28 for a flow cytometer analysis. Biopsy specimens were obtained at the time of presumed AR episodes and on day 28 after transplantation. RESULTS: The PD patients had a higher frequency of AR (37.5% in PD vs 9.1% in HD patients, P = 0.034). In contrast, two HD patients showed graft loss at 18 and 30 months after transplantation. The increases of CD3, CD19, CD4 and CD4+ CD28+ cells in the PD patients occurred earlier than in the HD patients and the numbers of these cells in the PD group were higher than those in the HD between days 3-28 after transplantation, most significantly on day 7. CONCLUSIONS: These findings suggest that the PD patients with similar clinical characteristics could potentially have a higher immunocompetence and immune responsiveness associated with a higher rate of AR in the early stage of renal transplantation when compared with the HD patients.