Clinical, tomographic, and postmortem aspects of a rare congenital Dicephalus Monauchenos Iniodymus in a Nelore calf produced in vitro from Brazil: case report / Aspectos clínicos, tomográficos e pós-morte de um raro Dicephalus Monauchenos Iniodymus congênito em um bezerro Nelore produzido in vitro no Brasil: relato de caso

The aim of this work was to report the occurrence of dicephalus iniodymus monauchenos in a Nellore newborn. A three-days old calf, from in vitro production, with duplication of the head and a history of cesarean birth was attended. On physical examination, the dicephalus, iniodymus and monauchenos, which were almost the same size and shape, had four eyes and four ears. Computed tomography showed the presence of two skulls fused with a common occipital foramen, two nasopharynxes, oropharynxes with the presence of a cleft lip and a cleft palate in the right head, which continued in a single esophagus and a single trachea. At necropsy, the presence of duplication of the cerebrum and cerebellum was observed, with union of the parts in the region of the trapezoid body of the brainstem and continued as a single spinal cord. This study characterizes the clinical, tomographic, and necropsy findings of a dicephalus Nelore neonate.(AU)

O objetivo deste trabalho foi relatar a ocorrência de Dicephalus Iniodymus Monauchenos em um neonato da raça Nelore de produção in vitro. Foi atendida uma fêmea bovina, de três dias de idade, com duplicação das cabeças e histórico de nascimento por meio de cesariana. No exame físico, observou-se a dicefalia, Iniodymus e Monauchenos, apresentando quatro olhos e quatro orelhas. Na tomografia computadorizada, constatou-se a presença de dois crânios fundidos com um forame occipital comum, duas nasofaringes, orofaringes com presença de lábio leporino e fenda palatina na cabeça direita, que continuavam em um único esôfago e em uma única traqueia. Na necropsia, observou-se a presença de duplicação do encéfalo e cerebelo, com união das partes na região do corpo trapezoide do tronco encefálico, que continuavam como uma única medula espinhal. Este estudo caracteriza os achados clínicos, tomográficos e de necropsia de um neonato Nelore dicefálico.(AU)

First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Living Related Renal Transplantation Using a Saphenous Vein Graft: A Case Report.

We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein. A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014. A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography. As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation. When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.

Hemangiossarcoma ocular em um equino: relato de caso / Equine ocular hemangiosarcoma: case report

O hemangiossarcoma ocular na espécie equina é um tumor maligno, raro e agressivo, de origem vascular endotelial. No presente trabalho, descreve-se um caso de hemangiossarcoma ocular em uma égua de 10 anos que apresentava secreção serossanguinolenta advinda de uma massa, acometendo a conjuntiva bulbar e a terceira pálpebra do olho direito. O diagnóstico foi realizado com base na avaliação histopatológica e na imuno-histoquímica. Foi realizada a enucleação, assim como a completa excisão cirúrgica do tecido acometido, não sendo observada, após seis meses da terapia, a recidiva ou a metástase da lesão.

Equine ocular hemangiosarcoma is a rare and aggressive malignant tumor of vascular endothelial origin. We describe a case of ocular hemangiosarcoma in a 10-year-old mare with serosanguineous secretion arising from a mass involving the bulbar conjunctiva and third eyelid of the right eye. The diagnosis was based on histopathological evaluation and immunohistochemistry. Enucleation was performed as complete surgical excision of the affected tissue, with no recurrence or metastasis of the lesion being observed after six months of.

Transplacental Transmission of Ovine Herpesvirus 2 in Cattle with Sheep-associated Malignant Catarrhal Fever.

Sheep-associated malignant catarrhal fever (SA-MCF) is an important infectious disease of ruminants worldwide that is caused by ovine herpesvirus 2 (OvHV-2). OvHV-2 is transmitted predominantly by contact between infected and susceptible hosts, while the documentation of vertical transmission is rare. This report presents the pathological and molecular findings associated with transplacental transmission of OvHV-2 in cattle. Two Girolanda cows with corneal oedema, lethargy, mucopurulent nasal discharge and ulcerative stomatitis died spontaneously; one of these was pregnant with a 4-month-old fetus. Significant pathological findings included widespread lymphoplasmacytic necrotizing vasculitis and lymphoplasmacytic accumulations in several organs of both cows and the fetus. A polymerase chain reaction that targeted the tegument protein gene of OvHV-2 amplified viral DNA from the brain of the pregnant cow and her fetus, as well as from the kidney of the pregnant cow. The pathological findings observed in the cow and her fetus, together with the presence of OvHV-2 DNA in tissues of these animals, are suggestive of transplacental transmission of OvHV-2 in SA-MCF in cattle.

Evaluation of 18S rDNA PCR assay using skin fragments as a diagnostic test for Trypanosoma caninum.

Trypanosoma caninum is a new species that has been recently identified in Brazil and infects domestic dogs. To date, no accurate diagnostic assays for this parasite have been established; thus, our aim was to evaluate more than one type of PCR for the diagnosis and molecular screening of T. caninum in 229 dogs living in Rio de Janeiro state. The tests were based on the amplification and sequencing of the 18S ribosomal DNA (rDNA) gene using healthy skin fragments. Additionally, PCR amplification of the kDNA minicircles region specific to the Leishmania genus was performed. The PCR results were compared with those of culture-based analysis performed with the same specimen. Using cultures, T. caninum and Leishmania chagasi were isolated from 11 and 12 dogs, respectively, whereas the 18S rDNA PCR assay detected parasitic infection in 35 dogs. Among these, 25 dogs showed an amplification pattern similar to T. caninum and 10 showed a pattern similar to L. chagasi; these results were confirmed by sequencing analysis. The kDNA PCR analysis showed that 14 dogs were positive for Leishmania infection. Of these, 2 dogs showed negative culture results and 12 were positive for L. chagasi, including 4 with negative 18S rDNA PCR results. Thus far, culture-based testing has been the only tool used successfully for T. caninum diagnosis. Our results demonstrate that 18S rDNA PCR-based test should be a useful diagnostic tool, particularly for distinguishing between T. caninum and L. chagasi infections in areas where these 2 parasites co-exist.

Clinical outcomes of recipients with aplastic bone disease after renal transplantation.

OBJECTIVES: We expect that if chronic renal failure (CRF) is improved after renal transplantation (RTx), dialysis osteopathy bone lesions would also recover to normal. Nevertheless, it is controversial whether bone lesions really improve after RTx. In this study, we evaluated whether pathological dialysis osteopathy improved after RTx. MATERIALS AND METHODS: The 84 patients who had undergone living related RTx had also undergone a bone biopsy (Bx) since January 2004, including 13 (16.0%) with a diagnosis of aplastic osteopathy. They included 7 men and 6 women. The average hemodialysis (HD) period was 40.3 months. The immunosuppression was tacrolimus (FK); mycophenalate mofetil (MMF) and steroid. We examined Ca, P, intact-PTH (i-PTH), metabolic bone markers, and bone density (DXA) before and 1 year after RTx. In addition, a Bx was performed after having osteal labeling twice before Bx. In addition 2 cases (15.3%) also underwent a Bx after RTx. RESULTS: All cases survive with well functioning renal grafts. The mean levels of Ca and P before RTx were 8.7 mg/mL and 6.6 mg/dL, respectively. The mean i-PTH level was 137.8 pg/mL before RTx and of alkaline phosphatase (ALP) was 202.1 U/L before RTx. The total density and % age match of DXA before RTx averaged 398.7 mg/ccm and 96.7%, respectively. The mean bone volume fraction (BV/TV: Bone Volume/Tissue Volume) before RTx was 17.2%. The mean osteoid volume (OV/TV) before RTx was 2.7%. The mean fibrosis volume (Fb.V/TV) before RTx was 0%. The mean bone formation rate (BFR/BV) before RTx was 2.1 %/y. Two cases were also pathologically diagnosed as renal osteodystrophy at 1 year after RTx: 1 case was mixed type, and another was osteomalacia, which was accompanied by a lumbar compression fracture (Fx) during the clinical course. CONCLUSIONS: Bone metabolism in patients with aplastic ROD histologically improved at 1 year after RTx, presumably due to good renal transplant function. However, it is unknown whether both hypophosphatemia and decrease of FGF-23 improved bone However, patients with aplastic ROD were not completely normalized histologically at 1 year after RTx.

Lack of antibodies against the antigen domain 2 epitope of cytomegalovirus (CMV) glycoprotein B is associated with CMV disease after renal transplantation in recipients having the same glycoprotein H serotypes as their donors.

Cytomegalovirus (CMV) reinfection of seropositive individuals has been associated with adverse outcomes in organ transplantation and is a frequent cause of congenital infection. Previously we demonstrated that mismatching of CMV glycoprotein H (gH) serotypes was associated with CMV disease after renal transplantation. Because the antigen domain 2 (AD2) epitope of glycoprotein B (gB) is conserved among CMV isolates and is one of the known targets of neutralizing antibodies, in this study we investigated whether antibodies against the epitope contribute to protection from CMV reinfection in renal transplantation, irrespective of gH serological matching. For this purpose, the gB and gH serology and clinical outcomes were analyzed retrospectively for 77 transplant recipients in the donor positive/recipient positive setting, who were managed by preemptive strategy. We found that there was a good negative correlation between the numbers of antigenemia-positive cells and the levels of antibodies against gB AD2 in the CMV-gH antibody matched group, but not in the CMV-gH antibody mismatched group. None of the recipients with antibodies against both gB AD2 and strain-specific epitopes of gH have experienced CMV disease during 6 month after transplantation, while 28% of those who lacked either/both antibody response needed preemptive therapy. Because the outcome was statistically significant, antibodies against gB AD2 can be a useful indicator to predict emergence of CMV disease for preemptive therapy, in addition to antibodies against the mismatched gH types.

Confocal Raman and electronic microscopy studies on the topotactic conversion of calcium carbonate from Pomacea lineate shells into hydroxyapatite bioceramic materials in phosphate media.

Conversion of Pomacea lineate shells into hydroxyapatite (HA) bioceramic materials was investigated by their in vitro treatment with phosphate solutions, at room temperature. Confocal Raman microscopy revealed that the conversion proceeds at distinct rates through the nacreous or periostracum sides of the shell. The conversion can be accelerated using powdered samples, yielding biocompatible materials of great interest in biomedicine.

Isolation of Trypanosoma caninum in domestic dogs in Rio de Janeiro, Brazil.

SUMMARY: The domestic dog's involvement with different members of the Trypanosomatidae family has been the focus of several studies due to this animal's close proximity to man. Recently this animal has been infected by a new Trypanosoma species (T. caninum), described in Rio de Janeiro and 19 similar isolates were later obtained. The objective of this study was to identify these isolates. All samples were isolated from intact skin cultures and analysed morphologically, by biochemical isoenzyme electrophoresis assays and by several molecular PCR assays. Additionally, anti-Leishmania sp. antibodies were assessed using the indirect Immunofluorescence Antibody Test (IFAT) in all animals. The methodologies employed to identify the isolates, including partial nucleotide sequences of 18S rRNA gene, indicated patterns identical to T. caninum and patterns different from the other species, including T. cruzi and T. rangeli samples. A phylogenetic tree constructed with the partial 18S ribosomal sequence shows that T. caninum is clustered with T. pestanai. Ten (52.6%) animals presented anti-Leishmania sp. antibodies with titres varying from 1:40 to 1:320. Thus, the hypothesis that this protozoan has disseminated among the dogs in Rio de Janeiro must be considered. The importance of a correct diagnosis in those animals and the possible consequences in the areas where visceral leishmaniasis is found are discussed here.

Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells.

Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express beta-galactosidase (beta-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased beta-gal mRNA expression and beta-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.

Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.

Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.

Thickening of the peritubular capillary basement membrane is a useful diagnostic marker of chronic rejection in renal allografts.

In kidney transplantation, the multilayering of the peritubular capillary basement membrane (MLPTC) in electron microscopy (EM) has been recognized as a feature of chronic rejection (CR). In this study, thickening of the peritubular capillary (PTC) basement membrane was evaluated by light microscopy (LM) to determine whether it corresponds to the MLPTC in EM and whether it can be used as a diagnostic marker of CR. Forty-eight patients with late renal allograft were divided into chronic allograft nephropathy (CAN) with CR (Group 1, n = 23), CAN without CR (Group 2, n = 19) and CAN-free (Group 3, n = 6). The thickening of the PTC basement membrane (ptcbm) was scored from grades 0 to 2 (ptcbm score), and the MLPTC thickness was measured in EM. Interobserver agreement on ptcbm scores was statistically significant (Kappa coefficient = 0.63). LM and EM lesions corresponded very well. The ptcbm score was highest in Group 1, and ptcbm2 corresponded closely with CR. Group 1 showed significantly thicker MLPTC than Groups 2 and 3. The results validated the usefulness of the ptcbm score and suggested that the thickening of the PTC basement membrane can be a novel diagnostic marker of CR.

Synthesis of pyrophosphate-containing compounds that stimulate Vgamma2Vdelta2 T cells: application to cancer immunotherapy.

Human Vgamma2Vdelta2 T cells recognize nonpeptide antigens, such as isoprenoid pyrophosphomonoester intermediates, alkylamine compounds, and bisphosphonate drugs, as well as some tumor cells. Although attempts have been made to derive novel cancer immunotherapies based on the discovery of these unconventional antigens, effective therapies remain to be developed. Here, we synthesized a series of pyrophosphate-containing compounds and examined the chemical requirements for the recognition of pyrophosphomonoester antigens by gammadelta T cells. The structural analysis clearly demonstrated that a proximal methylene moiety plays a crucial role in the stimulatory activity of the antigens. For optimal gammadelta T cell proliferation, we find that the use of human serum albumin was preferred and that pyrophosphomonoesters were superior to nitrogen-containing bisphosphonate compounds. Using these techniques, we have successfully expanded gammadelta T cells from healthy donors as well as from cancer patients using one of the most active compounds, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). The resulting expanded gammadelta T cells exhibited potent, cytotoxic activity against a wide variety of tumor cell lines. Even gammadelta T cells from a patient with advanced liver carcinoma efficiently responded to 2M3B1PP and exhibited strong cytotoxic activity against tumor cells. The pretreatment of tumor cells with nonpeptide antigens was essential for efficient cytotoxicity via TCR-gammadelta. The present study suggests a novel strategy for cancer immunotherapy using synthetic small pyrophosphate-containing compounds and nitrogen-containing bisphosphonates.

Evaluation of immunosuppressive regimens in ABO-incompatible living kidney transplantation--single center analysis.

Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKT), yet no single method has emerged as the best. We have made several substantial changes to our ABO-ILKT protocol over the past decade and a half and have attempted to determine whether the changes in immunosuppressive agents have resulted in a better outcome. We used methylprednisolone (MP), cyclosporine (CsA), azathioprine (AZ), antilymphocyte globulin (ALG) and deoxyspergualine (DSG) in the 105 cases of ABO-ILKT (group 1) between 1989 and 1999, and MP, tacrolimus (FK506), mycophenolate mofetil (MMF) in the 117 cases of ABO-ILKT (group 2) between 2000 and 2004. We compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1- and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.

Improved outcomes of renal transplantation from cardiac death donors: a 30-year single center experience.

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.

Analysis of the healthy rabbit lens surface using MAC Mode atomic force microscopy.

In this investigation healthy rabbit crystalline lenses were characterized by atomic force microscopy (AFM). The lenses were cut in slices with thickness with 1mm and thus, put after cortex distinct regions of nucleus and cortex for AFM examination. AFM analysis were carried out using a PicoSPM I operating in Mac Mode. We obtained topographic images of rabbit lenses and a quantitative analysis of the width and height of fibers for nucleus and cortex regions. The longitudinal section analysis of fibers in the nucleus region indicated structures with an average width of 200nm and average height of 200nm. The intershells distance was determined as 4microm. Fiber cell cross-section dimensions, longitudinal and transverse widths, could be estimated in these regions from the AFM images. Structures with average widths as small as 1.0microm are observed in the nucleus; the intershell distance is 4.0microm. In cortical regions, hexagonal structures with average longitudinal and transverse widths of 5.0mum and 3.0mum, respectively, were identified. Three-dimensional images of tissue sections with resolution on a nanometer scale were obtained. The potential of AFM analysis for characterizing healthy and pathologic lens tissues is discussed.

A pathological analysis of lymphatic vessels in early renal allograft.

Lymphatic vessels are an essential part of the immunological response. Nevertheless, little is known about the pathology of renal transplant rejection. In part the reason may be not distinguishing peritubular capillaries from lymphatic vessels by periodic acid-Schiff (PAS) staining. This study examined the morphology of lymphatic vessels in early renal allografts using double staining with PAS and podoplanin. The 41 cases were divided into four categories: (I) acute antibody-mediated rejection, (II) acute cellular rejection, (III) peritubular capillaritis only, and (IV) controls. I through III had the evidence of peritubular capillaritis exceeding grade 1 on a biopsy obtained an average of 17.3 +/- 5.5 days after kidney transplantation. In addition, each lymphatic vessel density (LVD) and nodular lesion of lymphocytes (NL) were quantified as the number of each podoplanin-positive vascular profiles and NL per unit area of cortex measured Lumina Vision (Mitani). The average of the LVD was 73.0, 35.1, 37.1, and 8.1 per 10 mm2 for groups I to IV and the average of NL was 2.8, 5.5, 1.3, 0.9, respectively. There was a significant correlation between LVD and NL. NL showed a strong relation to the accumulation of lymphocytes in lymphatic vessels (AL); 22% of the AL scores were greater than the peritubular capillaritis grade. We found lymphatic vessels to be strongly associated with any kind of inflammatory process that occurred unexpectedly soon after kidney transplantation. In addition, to avoid misdiagnosis of peritubular capillaritis, NL in early renal allograft must especially be excluded.

Safety analysis after tacrolimus immunosuppression in renal transplant recipients in Japan: 5-year results in >1500 patients.

Tacrolimus was approved in Japan in April 1996 for the prevention of allograft rejection in patients receiving kidney transplants. There has been a concern that immunosuppressive therapy may be associated with cardiovascular and metabolic complications, including hyperlipidemia, hypertension, and posttransplant diabetes mellitus. A multicenter (59 institutions) study was conducted in Japan in patients who underwent renal transplantation and received tacrolimus immunosuppression. Patients were followed for >5 years, from April 1996 to December 2002. Of the 1569 patients enrolled, 1542 were evaluated. In this analysis, graft survival rate and medication usage patterns of antihyperlipidemics, antihypertensives, insulin, and oral hypoglycemics were observed for >5 years in patients receiving tacrolimus immunosuppression. The graft survival rates of patients requiring antihyperlipidemic therapy and experiencing acute rejection were significantly lower compared with all other patients (P < .05). The risk of graft rejection was significantly greater in patients with cardiovascular complications requiring antihyperlipidemics or antihypertensives. Graft survival was significantly lower in patients with acute rejection and antihyperlipidemic therapy than in other patients.

Long-term results of tacrolimus therapy for renal transplantation in patients with diabetic nephropathy in Japan.

In Japan, the number of kidney transplants for the patients with diabetic nephropathy is limited because of an extreme organ shortage and poor patient and graft survival rates. We analyzed the 5-year outcomes in kidney transplant recipients treated with tacrolimus with (group 1; n = 53) and without a diagnosis of diabetic nephropathy (group 2; n = 1432). We also investigated outcomes in patients who received simultaneous pancreas and kidney transplants since 2000 (group 3; n = 15). Patients in group 1 were older than those in group 2, with a shorter duration of pretransplant dialysis (P = .0001). Five-year patient survival rates in groups 1 and 2 were 89.7% and 97.9%, respectively (P = .13), and 5-year graft survival rates were 89.6% and 94.8%, respectively (P = .44). The incidence of acute rejection within 3 months of transplantation was 28.3% in group 1 and 29.2% in group 2 (P = .98). Tacrolimus-based induction therapy was used in 13 of the 15 group 3 cases. Both kidney and pancreas grafts are surviving to date in all but one of the group 3 patients; one patient had the pancreas removed due to venous thrombosis at 7 days. It was concluded that tacrolimus-based therapy resulted in excellent 5-year outcomes in patients who had kidney transplantation because of diabetic nephropathy, despite the higher risks associated with this condition. Tacrolimus was also beneficial in association with simultaneous pancreas and kidney transplantation. These data encourage us to perform kidney transplantation in patients with diabetic nephropathy.