Helicobacter cinaedi bacteremia in four renal transplant patients: clinical features and an important suggestion regarding the route of infection.

Helicobacter cinaedi can cause bacteremia mainly in immunocompromised patients. We present the clinical characteristics of H. cinaedi bacteremia in 4 renal transplant patients. Interestingly, all cases showed triggers of bacterial translocation: 2 cases developed after colonic perforation caused by diverticulitis, 1 case developed post cholecystectomy, and the remaining patient had chronic diarrhea. Accordingly, bacterial translocation caused by severe gastrointestinal complication could be a cause of H. cinaedi bacteremia.

A patient with pregnancy-related acute abdomen after hemodialysis for over 18 years.

Because pregnancy is rare in women with end-stage renal disease, dialysis patients have not been reported to present with acute abdominal symptoms related to pregnancy including ectopic pregnancy. A 41-year-old woman treated with hemodialysis for over 18 years was brought to the emergency room at our institution because of acute abdominal pain. Ultrasonography detected an abdominal fluid collection, and her anemia had worsened (hematocrit 18%). Emergency laparoscopic exploration disclosed a hemorrhagic corpus luteum of pregnancy, causing ovarian bleeding on the left. Coagulation of bleeding points was carried out. At this time, pregnancy at 7 weeks of gestation was discovered. After the procedures, hemodialysis frequency was increased to 5 times weekly, and an erythropoietin derivative was administered to maintain a hematocrit above 30%. The patient developed no hypertension. At 33 weeks of gestation, cesarean section was performed because of a decrease in amniotic fluid and frequent late deceleration of the fetal heart rate. A live baby girl weighing 1,422 g was born. The successful pregnancy reflects remarkable progress in dialysis technology. Pregnancy, then, can underlie an acute abdomen in childbearing-age women (14 - 44 years old) undergoing long-term dialysis.

A case of trichilemmal carcinoma with distant metastases in a kidney transplantation patient.

Transplant recipients receiving immunosuppressants are at a high risk of cancer, especially skin cancer. Trichilemmal carcinoma is comparatively rare compared with other skin cancers. We report here a first case of trichilemmal carcinoma arising in a kidney transplant recipient. A 63-year-old man who had undergone a living donor renal transplantation at the age of 50 years presented with a 15 × 10 mm lesion on his forehead. The pathological diagnosis after resection was trichilemmal carcinoma. Distant metastases involving the lymph nodes, lung, and liver occurred, and the patient died. Given that trichilemmal carcinoma generally has an indolent clinical course and a low metastatic potential, the present case of trichilemmal carcinoma with an aggressive course resulting in distant metastases is rare.

Colovesical Fistula After Renal Transplantation: Case Report.

Colovesical fistula is a relatively rare condition that is primarily related to diverticular disease. There are few reports of colovesical fistula after renal transplantation. We report of a 53-year-old man who was diagnosed with colovesical fistula after recurrent urinary tract infection, 5 months after undergoing cadaveric renal transplantation. Laparoscopic partial resection of the sigmoid colon with the use of the Hartmann procedure was performed. Six months after that surgery, there was no evidence of recurrent urinary tract infection and the patient's renal graft function was preserved. Physicians should keep colovesical fistula in mind as a cause of recurrent urinary tract infection in renal transplant recipients, especially in those with a history of diverticular disease.

Cell-mediated graft rejection observed in two lines of human histocompatibility leukocyte antigen class I transgenic mice.

BACKGROUND: Human histocompatibility leukocyte antigen (HLA) class I molecules are essential for graft rejection. However, to determine the specific role of these molecules in clinical situations is difficult. We investigated the applicability of HLA class I transgenic mice (C3H.B35 and C3H.B51) for elucidation of the role of HLA class I molecules. METHODS: Skin or heart grafts were transplanted. Cytotoxic T cells (CTL) of C3H.B51 against C3H.B35 were generated and their cytotoxicity against various transfectant cell lines was determined. RESULTS: C3H.B35 skin and heart grafted to C3H.B51 were rejected within 17 and 28 days, respectively. Cytotoxic T cells generated from C3H.B51 showed cytotoxicity against a HLA-B*3501-transfectant cell line that did not express H-2 molecule, which indicates that these cytotoxic T cells recognize HLA-B35 molecules directly without H-2 restriction. CONCLUSION: Our results suggest that C3H.B51 recognize C3H.B35 grafts as allo-MHC class I-incompatible grafts, and these mice are valuable to elucidate the role of HLA class I molecules in transplantation.

Endotoxin impairs the response of rabbit mesenteric artery to electrical stimulation via a prejunctional mechanism.

1. The effect of E. coli lipopolysaccharide (LPS) on sympathetic neuro-effector transmission was studied in the rabbit mesenteric artery. The experiments were performed on artery rings isolated 5 or 20 h after intravenous treatment with LPS or saline as well as on artery rings isolated from non-treated rabbits (for assessment of the effect of in vitro preincubation with LPS). In most experiments, neural elements in the arteries were stimulated electrically (10 V, 2 ms, 1-32 Hz). 2. Preincubation with LPS (10 micrograms ml-1) for 5 or 20 h had no effect on the contraction responses of endothelium-intact artery rings to electrical stimulation. In contrast, in vivo intravenous pretreatment with LPS (10 micrograms) led to an inhibition of the contraction; LPS elicited this effect when injected 20 h, but not 5 h, before the experiment. The effect of LPS was eliminated in artery rings isolated from animals receiving an inhibitor of protein synthesis (actinomycin D or cycloheximide) before treatment with LPS. LPS (injected 20 h before the experiment) had no effect on the concentration-response curves for exogenous noradrenaline and tyramine in endothelium-intact artery rings. 3. The inhibition of electrically induced contractions produced by LPS treatment in endothelium-intact artery rings was attenuated by atropine and yohimbine, but not by phentolamine. Yohimbine plus atropine restored the depressed contraction to the normal level. Clonidine and acetylcholine mimicked the effect of LPS in endothelium-intact artery rings isolated from saline-treated animals. 4. When steady-state contractions were induced by 5 min of stimulation at 16 Hz, acetylcholine or clonidine reduced the contraction in endothelium-denuded artery rings from both saline-treated rabbits and animals receiving LPS 20 h before the experiment. The reduction produced by acetylcholine or clonidine of the contraction in artery rings from LPS-treated rabbits was significantly greater than in artery rings from saline-treated animals.5. These results suggest that treatment of rabbits with LPS inhibits noradrenaline release from sympathetic nerve endings via increased sensitivity of both prejunctional inhibitory muscarinic receptors and x2-adrenoceptors in mesenteric arteries. They also suggest that the effect of LPS is independent of endothelial cells but linked to protein synthesis.

Stimulation of beta-adrenoceptor enhances sensitivity to cisplatin in non-small cell lung cancer cell lines.

Cisplatin is a key drug in chemotherapy for lung cancer. It has been reported that intracellular accumulation of cisplatin is an important step as a determinant for resistance to cisplatin, which may be modulated by Na+, K+-ATPase activity. And it has been reported that beta-adrenoceptor agonists modulate the Na+, K+-ATPase in some organs. In this study, the effects of a beta-adrenoceptor agonist and an antagonist on membrane Na+, K+-ATPase activity were evaluated using human non-small cell (NSCLC) lung cancer cell lines. In the NSCLC cell lines, sensitivity to cisplatin was improved by treatment with isoproterenol. Na+, K+-ATPase was activated and intracellular accumulation of cisplatin increased with the treatment. But the antagonist, propranolol, did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. These results suggest that beta-adrenoceptors may be one of the determinant for sensitivity to cisplatin in NSCLC, but endogenous catecholamine dose not play a role in the intracellular accumulation of cisplatin in these cell lines. Exogenous beta-adrenoceptor agonists may improve the antitumor effect of chemotherapy involving cisplatin.

Progress reports on immune gene therapy for stage IV renal cell cancer using lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced autologous renal cancer cells.

There is no effective treatment for patients with stage IV renal cell cancer (RCC), although the introduction of new therapy is imminent. Cancer gene therapy is currently considered to be one of the most promising therapeutic modalities in the field of cancer treatment. Based on the results of animal studies, vaccination using autologous granulocyte-macrophage colony-stimulating factor-transduced renal cancer cells appears promising. Before initiating a clinical study using an ex vivo gene-transduced autologous cell vaccine-based immunogene therapy for RCC in Japan, in 1992 we initially planned a Japanese version of a clinical protocol in collaboration with a US group. In 1993, the original protocol was refined. We performed five preclinical qualification studies using RCC nephrectomy specimens from patients in 1997, and the results showed that preparation of RCC cells for autologous vaccines at the Clinical Cell Technology Facility, Research Hospital of the Institute of Medical Science, University of Tokyo, was feasible. Subsequently in August 1998, the Ministry of Health and Welfare and the Ministry of Education, Science, Culture, and Sport approved our clinical protocol. We have recruited two patients with stage IV RCC to our study so far. Here we report the background to the initiation of cancer gene therapy in Japan.

Exposure to sorbitol induces resistance to cisplatin in human non-small-cell lung cancer cell lines.

Cisplatin is the most active anticancer agent for lung cancer. It has been reported that intracellular accumulation of cisplatin is important in determining resistance to cisplatin, which may be modulated by Na+, K(+)-ATPase activity. On the other hand, it is well-known that sorbitol, a metabolite of glucose mediated by aldose reductase, reduces Na+, K(+)-ATPase in diabetic neuropathy. In this study, the effect of exogenous sorbitol on Na+, K(+)-ATPase activity and sensitivity to cisplatin was evaluated using human non-small-cell lung cancer (NSCLC) cell lines. In the NSCLC cell lines, EBC-1, PC-3, and RERF-LC-MS the cytotoxicities of cisplatin were impaired by exposure to sorbitol in these cell lines. Na+, K(+)-ATPase was inactivated and intracellular accumulation of cisplatin was decreased by the exposure. These results suggest that accumulation of sorbitol may induce resistance to cisplatin in NSCLC cells, and diabetes poorly controlled may be one of the determinants of the antitumor effect of cisplatin in NSCLC.

Primary prostatic lymphoma of mucosa-associated lymphoid tissue.

We present a case of primary prostatic lymphoma referring to a 57-year-old man, who was admitted with the symptom of bladder outlet obstruction, and had a history of urination difficulty for two years. The symptoms and signs were compatible with a diagnosis of benign prostatic hypertrophy (BPH). The pathology of the specimen obtained from transurethral prostatectomy showed B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The patient has been asymptomatic and under complete remission after completion of chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine and prednisone for 6 cycles.

Advantages of triple therapy with mizoribine, cyclosporine and prednisolone over other types of triple and/or double therapy including cyclosporine for renal transplantation.

Mizoribine (Mz) is an analogue of azathioprine (Az) with less hepatotoxicity, being extensively used as immunosuppressant in place of the latter agent especially in Japan. However, careful comparative studies of mizoribine (Mz), cyclosporine (Cy), and prednisolone (Pr) versus azathioprine (Az), Cy and Pr or Cy and Pr in renal allotranspalnt patients have not been reported. Retrospectively we compared triple therapy with Mz, Cy, and Pr (group I, n = 50) to triple therapy with Az, Cy and Pr (group II, n = 13) and/or double therapy with Cy and Pr (group III, n = 11) in one-haplotype-identical living related renal transplantations performed between Oct. 1984 through March 1989. Initial and maintenance doses of Cy in groups I and II were largely two thirds of those in group III. Patient and graft survival rates at 3 years in each group are 100% and 92% (group I), 100% and 91% (group II), and 91% and 82% (group III). There were no statistical differences in patient and graft survival rates between these three groups. The incidences of miscellaneous complications were the same in the groups. Bone marrow suppression, however, was significantly less in group I than in group II (P less than 0.005). Cy related nephrotoxicity was apparently less in groups I and II than in group III. Estimated US $5,000 in a year can be saved by immunosuppressive treatment in a patient of group I as compared to a patient in group III. Therefore, we conclude that triple therapy with Mz, Cy and Pr is superior to those with Az, Cy and Pr, and/or double therapy with Cy and Pr.

[Lipoprotein (a) and sclerotic changes in retinal arterioles].

Lipoprotein (a) (Lp(a)) has been considered an independent risk factor for arteriosclerotic disease and its role in retinal vascular changes was studied in this report. The study was made on 160 patients of age 54 and above. They were divided into four groups depending upon their clinical background with or without the presence of diabetes mellitus (DM) and cerebral infarction (CI). The retinal vascular status of the patients was studied by ophthalmoscopic examination and the findings were graded according to Scheie's classification. We found that all the patients with retinal arterial hypertension and arteriosclerosis had a significant by high level of serum Lp (a). Similarly, serum Lp (a) level was higher in the patients with DM and CI than in the control subjects. These findings suggested that Lp (a) might influence the pathological changes of senile retinal arterioles. Moreover, we found a positive linear correlation between Lp (a) and plasminogen in patients with CI.

[Role of neutrophils in warm renal ischemia and reperfusion injury in the rat].

This study attempts to determine whether the circulating neutrophils play a role in mediating injury resulting from renal ischemia, using rats treated with cyclophosphamide (CY) and/or granulocyte colony-stimulating factor (G-CSF). The neutrophil counts immediately before 60-minute ischemia decreased by 89% in the CY-treated rats in comparison with the untreated animals (p < 0.01). In the rats given G-CSF with CY, the neutrophil counts significantly increased over that of the CY-treated rats (p < 0.01). The serum creatinine level 24 hours after reperfusion amounted to 4.42 +/- 0.37 mg/dl in the control rats and 2.63 +/- 0.29 mg/dl in the CY-treated rats (p < 0.01). In 19 rats, 10 controls and the 9 CY-treated, the neutrophil counts immediately before ischemia correlated well with the serum creatinine levels 24 hours after reperfusion (r = 0.597; p < 0.01). Our results appear to indicate that neutrophils play an important role in warm ischemia and reperfusion injury of the kidney.

[Clinical studies on 228 renal transplants].

We studied patient survival and graft survival rates by dividing 228 renal transplants into seven groups according to their immunosuppressive regimen and the degree of histocompatibility. Both patient survival and graft survival rates of HLA identical sibling (Id Sib), living related transplantation with cyclosporin (CYA), transplantation with donor-specific transfusion and anti-lymphocyte globulin (DST.ALG) and cadaveric transplantation with cyclosporin (CYA.Cad) groups were better than those of living related transplantation with ALG, without DST (ALG), living related transplantation with azathioprine and steroid (Non-DST.Non-ALG) and cadaveric transplantation without cyclosporin (Conv.Cad) groups. The incidence and severity of acute rejection were lower in Id Sib, CYA, DST.ALG and CYA.Cad groups than in other groups. The incidence of infections was the highest in Conv.Cad group and that of fatal infections was higher in ALG, Non-DST.Non-ALG and Conv.Cad groups than in other groups. These results indicated that acute rejection and infection were two important factor that influenced the survival rates of these patients. Up to now, the graft survival rate of CYA.Cad group has been much improved as compared to that of Conv.Cad group and was better than those of ALG and Non-DST.Non-ALG groups. The fact urges us to promote more cadaveric renal transplantation in our country by virtue of ciclosporin.

Hand-assisted technique facilitates preserving graft viability in laparoscopic donor nephrectomy.

BACKGROUND: To achieve patient safety and minimal operative invasion in living kidney donor nephrectomy, we have performed hand-assisted laparoscopic donor nephrectomy (HALDoN) since 2006. AIM: The aim of this study was to evaluate the utility and the technique of HALDoN. METHOD: We analyzed 72 donors who underwent HALDoN from February 2008-August 2011. RESULTS: Including 8/72 donors who underwent right nephrectomy, all subjects completed HALDoN without conversion to an open procedure. None of the recipients suffered delayed graft function or an ureteric problem. Knife-to-removal time (KRT) was longer among cases with graft weight (GW) >200 g than GW ≤200 g: 176.5 ± 35.1 minutes vs 142 ± 18.7 minutes (P < .001). Longer KRT (>180 minutes) and right nephrectomy produced longer reperfusion-to-urine secretion time (RUT; P = .002 and P = .027, respectively). Grafts with double renal arteries (N = 10) also tended to show longer RUT (P = .058). In a case with an early renal arterial branch <1 cm from the aorta, we transected the vessel to achieve a single orifice of the artery using a stapling device. At 6 months the average value of decreased renal function of donors had recovered to about 70%. The incidence of complication was 8.3% but there was no life-threatening morbidity. CONCLUSION: The hand-assisted method could make the operating surgeon more confident to perform laparoscopic donor nephrectomy safely. HALDoN offers particular advantages for precise dissection using finger retraction and control of potential bleeding in the stages of vascular stapling and graft removal, preserving graft viability.