International geographic correlation study of the prevalence of disorders of male reproductive health.

STUDY QUESTION: Is there evidence at the population level of associations between different male genital disorders, outside Scandinavian countries? SUMMARY ANSWER: At an international scale, there is evidence for a number of correlations between rates of four male reproductive disorders (hypospadias, cryptorchidism, testicular cancer and low sperm concentration). WHAT IS KNOWN ALREADY: Some associations between these outcomes have been shown in studies focusing on individuals and mainly in Nordic European countries. These associations, together with histological evidence of a dysgenesis pattern in testicular tissue specimens, have generated the concept of the existence of a 'testicular dysgenesis syndrome' originating in utero. STUDY DESIGN, SIZE, DURATION: This is a geographical correlation study using cancer, malformations rates and sperm quality data collected between the years 1998 and 2005. PARTICIPANTS/MATERIALS, SETTING, METHODS: Incidence rates of testicular cancer were extracted from International Agency for Research on Cancer registries and Globocan, while cryptorchidism and hypospadias prevalence rates were obtained from EUROCAT and International Clearinghouse for Birth Defects Surveillance and Research registries. Sperm concentration data were extracted from recent studies using standardized methodology. A total of 39 registries and 9 sperm studies were selected. Non-parametric Spearman correlation tests were used to test the association between these four disorders. Correlations were computed for all registries together, for registries with high-quality matching coverage only and by continents. Sensitivity analyses were also conducted using data from prospective clinical studies to take into account potential bias related mainly to ascertainment of malformation rates. MAIN RESULTS AND THE ROLE OF CHANCE: We found positive correlations between testicular cancer and hypospadias (r = 0.32, P = 0.05) and between hypospadias and cryptorchidism (r = 0.70, P = 0.008). Stronger correlations were observed when using registries with high-quality matching coverage. Among these registries, differences between Europe and the rest of the world appeared (the positive correlation between testicular cancer and cryptorchidism was stronger outside Europe, r = 0.83, P = 0.01 compared with 0.40, P = 0.60 for European registries). A negative correlation between testicular cancer and sperm concentration was observed (r = -0.88, P = 0.002). These correlations support our initial hypothesis but remain only suggestive due to the intrinsic limitations in the study design (i.e. geographical correlation study) and do not allow causal inference. LIMITATIONS, REASONS FOR CAUTION: Differences in the ascertainment of malformations rates (definition, length of follow-up) make the international comparison difficult. The small number of registries for some conditions (cryptorchidism) or of studies (for sperm quality) and the absence of information about major risk factors such as ethnicity and socioeconomic status in the registries are also limitations. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are in agreement with results of studies focusing on individuals and suggest that shared risk factors are present in the populations studied.

Enlarged lymph nodes in the upper abdomen after liver transplantation: imaging features and clinical significance.

PURPOSE: Our aim was to review our single-centre experience regarding imaging features and pathological conditions arising from enlarged lymph nodes following orthotopic liver transplantation (OLD) and identify imaging features that may allow narrowing the differential diagnosis. MATERIALS AND METHODS: Between January 1997 and September 2008, 715 OLTs were performed at our Institution in 585 patients. In 19 patients (2.6 %) ultrasound (US) showed enlarged lymph nodes in the upper abdomen, and abdominal computed tomography (CT) was performed RESULTS: Histological results showed posttransplantation lymphoproliferative disorder (PTLD) in six patients (31.5 %), hepatic tumoral disease in six (31.5 %), disseminated systemic tuberculosis in one (5.2%) and sarcoidosis in one (5.2%). Histological results showed nonspecific reactive lymph node hyperplasia in five patients (26%). CONCLUSIONS: Detecting enlarged lymph nodes in the upper abdomen after liver transplantation is and infrequent occurrence; however, thorough imaging is required to detect and characterise a wide variety of disorders. Most of the time, enlarged lymph nodes will be related to posttransplantation lymphoproliferative disorder or tumoral recurrence.

Definitive diagnosis of neuroendocrine tumors using fine-needle aspiration-puncture guided by endoscopic ultrasonography.

BACKGROUND: The detection and diagnosis of neuroendocrine tumors (NETs) is challenging. Endoscopic ultrasonography (EUS) has a significant role in the detection of NETs suspected from clinical manifestations or imaging techniques, as well as in their precise localization and cytological confirmation using EUS-Fine-needle aspiration-puncture (FNA). OBJECTIVE: To assess the usefulness and precision of EUS-FNAP in the differential diagnosis and confirmation of NETs, in a retrospective review of our experience. PATIENTS AND METHODS: in a total of 55 patients with suspected NETs who underwent radial or sectorial EUS, 42 tumors were detected in 40 cases. EUS-FNA using a 22G needle was performed for 16 cases with suspected functional (hormonal disorders: 6 cases) and non-functional NETs (10 cases). Ki 67 or immunocytochemistry (ICC) testing was performed for all.There was confirmation in 9 cases (5 female and 4 male) with a mean age of 51 years (range: 41-81 years).All tumors were located in the pancreas except for one in the mediastinum and one in the rectum, with a mean size of 19 mm (range: 10-40 mm). RESULTS: There were no complications attributable to FNA. Sensitivity was 100% and both precision and PPV were 89%, as a false positive result suggested a diagnosis with NET during cytology that surgery finally revealed to be a pancreatic pseudopapillary solid tumor. CONCLUSIONS: EUS-FNA with a 22G needle for NETs has high sensitivity and PPV at cytological confirmation with few complications.

Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer.

Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15-20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC.

Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at 18F-FDG-PET/CT: prognostic implication of metabolic parameters and tumor markers.

BACKGROUND AND PURPOSE: Cholangiocarcinoma is an infrequent neoplasm barely studied with 18F-FDG-PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance. METHODS: Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses). RESULTS: Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R2 0.22-0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival. CONCLUSIONS: Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis.

Antral mass due to cytomegalovirus infection requiring gastrectomy in a liver transplant recipient.

The incidence of cytomegalovirus (CMV) infection after liver transplantation (LT) has decreased in recent years. Advances in immunosuppression and CMV prophylaxis have improved the management of CMV disease. Organ involvement is infrequent and gastrointestinal CMV disease is quite rare. Few cases of an antral mass due to CMV infection have been described; those reported to date have mostly been in patients with acquired immunodeficiency syndrome. We describe a case of a CMV-seronegative liver transplant patient who received a seropositive liver graft. Owing to gastrointestinal complaints, CMV prophylaxis was stopped one month after LT. The patient developed an antral mass due to CMV infection and an anastomotic biliary stricture. Antigenemia became negative with ganciclovir, but this treatment did not eliminate the mass. Ganciclovir resistance was ruled out as well as other causes of antral mass, especially malignancy. The patient finally required gastrectomy and hepaticojejunostomy. We conclude that CMV disease is less common today but should be included in the diagnosis of gastrointestinal mass after transplantation.

Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections.

OBJECTIVES: The kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue infection were studied. DESIGN: Serum, saliva, and urine samples were collected from 22 patients with clinical and confirmed dengue 3 virus infection during the outbreak in Havana City in 2001. They were tested by capture IgM (MAC-ELISA), IgA (AAC-ELISA), and IgE (EAC-ELISA) and IgG ELISA inhibition method (EIM) to detect specific dengue antibodies. RESULTS: Similar kinetics were observed in IgM, IgA, and IgG antibodies in saliva and IgA and IgG in urine samples from secondary cases compared with kinetics in serum samples, although the values were lower. No IgG antibody was detected in saliva and urine samples in primary cases and IgM antibody was not detected in urine samples from either primary or secondary infection. All secondary cases were positive for IgG in saliva and urine samples at day 7. The kinetics of specific IgE antibodies in primary and secondary cases were different. CONCLUSIONS: The kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infection were studied for the first time, showing its behavior and usefulness in dengue virus diagnosis. The specific IgE could play a role as a serological marker in secondary infections.

Preliminary results of treatment with pegylated interferon alpha 2A for chronic hepatitis C virus in kidney transplant candidates on hemodialysis.

INTRODUCTION: At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population. PATIENTS AND METHODS: Twelve noncirrhotic HCV-infected patients (10 men, 50 +/- 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 microg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases. RESULTS: Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients. CONCLUSIONS: Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.

Gastrointestinal complications in liver transplant recipients: MITOS study.

INTRODUCTION: Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. OBJECTIVE: The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. PATIENTS AND METHODS: This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. RESULTS: The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. CONCLUSIONS: The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Isolation of Campylobacter spp. from Three Species of Antarctic Penguins in Different Geographic Locations.

The presence of Campylobacter species was studied in three Antarctic penguin species, Adélie (Pygoscelis adeliae), chinstrap (Pygoscelis antarctica) and gentoo (Pygoscelis papua). A total of 390 penguins were captured in 12 different rookeries along the Antarctic Peninsula with differences in the amount of human visitation: six colonies were highly visited [Stranger Point, King George Island (P. papua and P. adeliae); Hannah Point, Livingston Island (P. papua and P. antarctica); Deception Island (P. antarctica); and Paradise Bay, Antarctic Peninsula (P. papua)], and six colonies were rarely visited [Devil's Point, Byers Peninsula, Livingston Island (P. papua); Cierva Cove, Antarctic Peninsula (P. papua); Rongé Island (P. papua and P. antarctica); Yalour Island (P. adeliae); and Avian Island (P. adeliae)]. A total of 23 strains were isolated from penguins from nine different rookeries. Campylobacter lari subsp. lari was isolated from eight samples (seven from P. papua and one from P. adeliae); C. lari subsp. concheus from 13 (ten from P. adeliae and three from P. antarctica) and C. volucris from two samples (both from P. papua). We did not find any significant differences in the prevalence of Campylobacter spp. between the populations in highly and rarely visited areas. This is the first report of C. lari subsp. concheus and C. volucris isolation from penguins in the Antarctic region.

Measuring biological responses at different levels of organisation to assess the effects of diffuse contamination derived from harbour and industrial activities in estuarine areas.

To evaluate the effects of diffuse contamination, biological measurements were applied in a scrap cargo harbour, a marina and an industrial area. Metal accumulation and biomarkers (survival in air, digestive gland and gonad histopathology, lysosomal membrane stability, intralysosomal metal accumulation, transcription of vitellogenin and MT20, peroxisome proliferation and micronuclei formation) were measured in transplanted mussels, together with metrics of benthic invertebrates. Benthic species were classified into ecological groups and univariate indexes were calculated. The marina showed high richness (16) and percentage of opportunistic species (55.1%) and low metal accumulation. Mussels in the scrap cargo harbour showed high metal accumulation, up-regulation of MT20 transcription, reduced health status (LP<6 min) and increased micronuclei frequencies (up to 11.3‰). At the industrial area, low species richness (4) and badly organised assemblages were detected and chemical analyses indicated significant amounts of bioavailable metals. Overall, selected biological measurements showed potential for the assessment of diffuse contamination.

[Implementation of a best practice guideline for the prevention of falls: Perception among hospitalized patients and its caregivers]. / Implantación de una guía de buenas prácticas para la prevención de caídas: percepción de los pacientes hospitalizados y sus cuidadores.

OBJECTIVE: To analyze the influence that the implementation of a fall prevention Best Practice Guideline (BPG) could have on the perception of patients and their caregivers about the utility of the activities implemented, about the care provided during admission and the adherence (the level of follow-up) to the recommendations received at discharge. MATERIAL AND METHOD: Design. Quasi-experimental study. Patients >65 years admitted≥48h to the Medical Area of the General Hospital of Albacete. SAMPLE: 104 subjects (consecutive sampling January-March 2013). Experimental group (EG). Patients admitted to BPG implementation units. Control group (CG). Usual care units. VARIABLES: Sociodemographic characteristics; previous and during admission falls, cognitive status (Pfeiffer); independence in daily life activities (ADLs); satisfaction with care and information provided, utility perceived, adherence to recommendations at discharge. DATA SOURCES: Interview and clinical history. Statistical analysis (SPSS 15.0). Descriptive and bivariant. Relative Risk. CI95%. RESULTS: 104 patients, EG 46.2% (48) and CG 53.8% (56). Women 51.9%, average age 79.9 years (s.d.=7.8). Pfeiffer 4,3 (s.d.=3.7). Previous falls 31.1%. In process, 1 fall in each group. There were statistically significant differences between EG/CG: age, cognitive status and independence in ADLs. In the EG was higher the percentage of perception about the usefulness of the recommendations to prevent falls (P<.001), greater adherence to them (P=0.0002), and to be very or quite satisfied with the information (P<.00004) and care received (P=.002). CONCLUSION: To implement recommendations according to an Evidence-based BPG to prevent falls in older people has shown, in users and caregivers, greater satisfaction, better perception of its usefulness and greater adherence to the recommendations.

Serological markers during dengue 3 primary and secondary infections.

BACKGROUND: The detection of the IgM antibody for the dengue virus in serum by ELISA has become one of the most important and useful methods for diagnosis of dengue using a single acute-phase serum sample. Currently, this system is an invaluable tool for the surveillance of dengue fever (DF) and dengue hemorrhagic fever (DHF). The usefulness of other serological markers such as IgA and IgE have been less studied. OBJECTIVE: To study the IgM, IgA and IgE specific antibody response in dengue 3 infected patients with different clinical picture and type of infection. STUDY DESIGN: One hundred and twenty-seven serum samples collected on days 5-7 at the onset of fever from clinically and serologically confirmed dengue cases were studied. Forty-two were classified as primary dengue fever cases, 48 as secondary dengue fever cases and 37 as secondary dengue hemorrhagic fever cases. All samples were tested by capture ELISA in order to detect dengue IgM, IgA and IgE antibodies. RESULTS AND CONCLUSIONS: In this study, significant differences were observed in the IgM, IgA and IgE response between the study groups. High IgA and IgE OD ratios in secondary dengue cases were found. The usefulness of serotype specific IgM antibody detection is also analyzed and discussed. A priority for future dengue research in terms of protection, recovery of infection and immunopathogenesis is to elucidate the role of these immunoglobulins. The cross reactivity response to IgM between dengue virus serotypes in primary and secondary cases should also be more studied.

Clinical and virological effects during two years of ongoing adefovir dipivoxil in the treatment of lamivudine-resistant chronic hepatitis B infection.

OBJECTIVE: Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. PATIENTS AND METHODS: Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. RESULTS: A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus-RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. CONCLUSIONS: Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

Liver Transplant Patient Carriers of Polymorphism Cyp3a5*1 Donors May Need More Doses of Tacrolimus From the First Month After Transplantation.

BACKGROUND: The aim of this work was to evaluate the CYP3A5:CYP3A5*1/CYP3A5*3 (6986A>G) polymorphism related to the pharmacokinetic characteristics of tacrolimus during the first 3 months after transplantation, analyzing both donor and recipient genotype, in liver transplant patients. METHODS: This retrospective, single-center, cohort study included patients who had been treated with tacrolimus monotherapy with or without corticoids (n = 67). Donors and recipients were genotyped for the CYP3A5*3 allele polymorphism (6986A>G) by use of a TaqMan polymerase chain reaction technique. The presence or absence of the *1 allele ("minor-allele") was analyzed for correlation with the tacrolimus dose-normalized ratio during the 3 months after transplantation. RESULTS: The following observations were obtained in the population studied: (1) Frequency of the minor allele*1 was much lower both in recipients (11.9% versus 88.1%) and donors (19.4% versus 80.6%), with no statistically significant differences between both distributions. (2) Recipient genotype for CYP3A5*1/*3-polymorphism had no influence in tacrolimus pharmacokinetics, with no differences between carriers and non-carriers of the minor-allele*1. (3) However, from the first month after transplantation, patients with grafts from donor carriers of minor allele*1 had lower concentration-dose ratios compared with patients with grafts from donor non-carriers of that allele (71.1 versus 119.3 and 90.5 versus 126.3, for 30 and 90 days after transplantation, respectively; P < .05). CONCLUSIONS: The presence of the CYP3A5-6986A>G-polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although the difference was statistically significant only for the first month after transplantation. This means that in liver transplant patients receiving grafts from donors carrying the CYP3A5*1-polymorphism, a larger dose of tacrolimus from the first month after transplantation would be needed. The evidence provided in this study showed no effect of the recipient genotype.

X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis.

Sprague-Dawley rats aged 1 or 15 days were irradiated with a single dose of 200 cGy X-rays and killed at different intervals from 3 to 48 hours (h). Dying cells were recognized by their shrunken and often fragmented nuclei and less damaged cytoplasm in the early stages. On the basis of immunocytochemical markers, dying cells probably represented a heterogeneous population which included neurons and immature cells. In rats aged 1 day the number of dying cells rapidly increased in the hippocampal complex with peak values 6 h after irradiation. This was followed by a gentle decrease to reach normal values 48 h after irradiation. The most severely affected regions were the subplate and the cellular layer of the subiculum, gyrus dentatus and hilus, and the stratum oriens and pyramidale of the hippocampus (CA1 more affected than CA2, and this more affected than CA3). X-ray-induced cell death was abolished with an injection of cycloheximide (2 micrograms/g i.p.) given at the time of irradiation. X-ray-induced cell death was not changed after the intraventricular administration of nerve growth factor (NGF; 10 micrograms in saline) at the time of irradiation. Cell death was not induced by X-irradiation in rats aged 15 days. These results indicate that X-ray-induced cell death in the hippocampal complex of the developing rat is subjected to determinate temporal and regional patterns of vulnerability; it is an active process mediated by protein synthesis but probably not dependent on NGF.

Heart and liver xenotransplantation under low-dose tacrolimus: graft survival after withdrawal of immunosuppression.

BACKGROUND: The hamster-to-rat xenotransplantation model is a useful model to investigate the features of extended host response to long-surviving xenografts. Early xenoantibody responses are T-cell independent and resistant to tacrolimus. Treatment with the combination of mofetil mycophenolate plus FK506 avoids acute xenograft rejection completely, but after withdrawal of immunosuppression hamster grafts are rejected by a process called late xenograft rejection (LXR). METHODS: Hamster hearts and livers were transplanted into Lewis rats. Grafted rats were treated with mofetil mycophenolate (25 mg/kg/day) for 8 days and FK506 (0.2 mg/kg/day) for 31 days. Serum IgM and IgG levels were determined by flow cytometry and interferon-gamma levels by ELISA. IgM, IgG, and C3 deposits were measured in tissue by immunofluorescence, and leukocyte infiltration was measured by immunoperoxidase staining. Results. Survival of heart and liver xenografts in the rats was 48+/-4 days and 63+/-8 days, respectively. After cessation of all immunosuppression, hearts were rejected in 18+/-4 days and livers in 33+/-8 days. Production sequences of xenoantibodies in the two organs differed substantially, especially 7 days after transplantation and at the moment of rejection. Quantification of interferon-gamma levels indicated that there were no significant changes after transplantation. Histological and immunohistochemical studies showed signs of humoral mechanism of LXR in rats undergoing heart transplantation and cellular mechanism of LXR in those that received a liver transplant. Conclusions. These observations suggest that rejection in the hamster-to-rat heart xenotransplantation model is mediated by a T cell-independent B-cell response to which a T cell-dependent B-cell response is added in LXR. In the liver xenotransplantation model, our hypothesis is that LXR is mediated by a mixed cell mechanism, involving lymphocytes CD4+ CD45RC+, macrophages, and cytotoxic T lymphocytes. In summary, we have demonstrated and compared the peculiar features of LXR in two different organs.

Studies with the Golgi method in central gangliogliomas and dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease).

The rapid Golgi method, combined with current optical and electronmicroscopical techniques, was used in three central gangliogliomas and in one dysplastic gangliocytoma of the cerebellum to study the morphology of ganglionic cells. Gangliogliomas were composed of bipolar, fusiform and radiate cells with dense core and clear vesicles in the perikaryon and cellular processes, the number of each cellular type varying from one case to another. These features, together with the fact that isodendritic neurons are considered to be phylogenetically old neurons, suggest that these tumours are composed of "primitive" neurons that are not homogeneous with regard to their morphology. In contrast, ganglionic cells in dysplastic gangliocytoma are huge cells with long, stereotyped neurites that establish unique asymmetric contacts with neighbouring perikarya and neurites by means of claw-shaped processes covered with synaptic buttons. These morphological characteristics are different from those of any other neuron of the CNS.

Nerve growth factor levels in normal human sera.

Nerve growth factor (NGF) is the best characterized of the neurotrophic factors, but there is incomplete information concerning its levels in body fluids. Normal values of NGF in serum from 157 normal subjects were determined by enzyme immunoassay (EIA). A mean NGF level of 194 +/- 25 pg ml-1 was obtained. There were no statistically significant variations with age, but the NGF level was significantly lower in females (112 +/- 31 pg ml-1) than in males (243 +/- 35 pg ml-1).

Naturally occurring cell death in the subicular complex and hippocampus in the rat during development.

Cell death in the subicular complex and hippocampus occurs from P0 to P7 in the rat. Dead cells first appear in the subcortical and subammonic plates, and predominate in the border region between the main regional subfields. Cell death in the cellular layers predominates in the subicular complex. CA1 and intermediate region between CA1 and CA3. Dead cells are almost absent in the upper plexiform layers and dentate gyrus.