Epidemiology and impact of Neospora caninum infection in three Queensland tropical dairy herds.

This study investigated the epidemiology of Neospora caninum in three tropical dairy herds in North Queensland, Australia. All animals in the herds were bled, and the sera were tested by ELISA for N. caninum antibodies. Herd records were examined, and the number of calves carried to term and the number of abortions which occurred over the lifetime of each animal were recorded to determine the abortion rate for each animal. Pedigrees were constructed for two of the herds to investigate whether vertical transmission was occurring. The seroprevalence of N. caninum ranged from 23% to 34%. The abortion rate in seropositive animals was significantly (p < 0.001) higher than in seronegative animals in all three herds (12-20.1% cf. 3.6-7%). Overall, the probability of a calf being seropositive was 3.5 times higher when the dam was also seropositive than when the dam was seronegative. Subsequent selective breeding employed by one herd reduced the N. caninum seroprevalence from 23% to 5% over a 9-year period. This study shows that N. caninum infection is prevalent in North Queensland dairy cattle, and both post-natal infection and vertical transmission are common.

Evaluation of a commercially available enzyme-linked immunosorbent assay for detecting antibodies to Fasciola hepatica and Fasciola gigantica in cattle, sheep and buffaloes in Australia.

A commercially available ELISA for detecting antibodies to liver fluke was evaluated for use in Australia. Milk and serum samples from cattle and sheep in which infection with Fasciola hepatica was confirmed by detection of eggs in faeces were used to estimate sensitivity. Similar samples collected from cattle and sheep outside the F. hepatica-endemic area were used to estimate specificity. The ELISA was also evaluated for detecting antibodies to F. hepatica in milk from sheep and antibodies to Fasciola gigantica in sera from cattle and buffaloes, but with small numbers of samples. In cattle, the sensitivity and specificity of the ELISA were 98.2% and 98.3% using serum and 97.7% and 99.3% using milk. In infected herds, 41.4% and 41.5% of animals were positive in the serum and milk ELISAs, respectively, whereas F. hepatica eggs were found in faecal samples from 26.5% of animals. In sheep, the sensitivity of the ELISA was 96.9% and the specificity was 99.4%. In infected flocks, 60.2% of animals were positive in the serum ELISA and F. hepatica eggs were found in faecal samples 52.2% of animals. There was perfect agreement in the ELISA between paired serum and milk samples collected from ewes. The assay detected antibodies in sera from cattle and buffaloes with natural and experimental F. gigantica infections. In the experimentally infected animals, antibodies were detected 2 weeks post-infection. We conclude that the ELISA will be a valuable tool for diagnosing F. hepatica infections in cattle and sheep. The assay may also be useful for diagnosing F. gigantica infections but further studies are required to establish sensitivity and specificity.

Cotton-wool exudates not observed in recipients of renal transplants treated with cyclosporine.

Retinal cotton-wool patches, not previously observed in bone marrow recipients, have been reported in three patients who received Sandimmun (cyclosporine) as prophylaxis for graft-versus-host-disease after bone marrow transplantation. These patients all had acute lymphoblastic leukemia and had received, in addition to the standard conditioning regimen, central nervous system irradiation before transplantation. We were thus prompted to examine 55 renal transplant recipients (15 of them prospectively) who were receiving cyclosporine for evidence of similar fundal changes. No cotton-wool patches were found in any of the renal transplant recipients.

The efficacy and tolerability of cyclosporine G in human kidney transplant recipients.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.

A randomized prospective trial of prophylactic immunosuppression with ATG-fresenius versus OKT3 after renal transplantation.

We carried out a randomized prospective trial to compare OKT3 (5 mg/d, 51 patients) with ATG-Fresenius (ATG-F, 4 mg/kg/d, 53 patients) for induction therapy after renal transplantation, concerning side effects, rejection, and infection incidence within a one year follow-up period. Concomitant immunosuppression included azathioprine/steroids from day 0 and cyclosporine A from day 4. OKT3 patients experienced significantly more and more-severe side effects, particularly pyrexia, headache, and pulmonary fluid overload. One-year graft survival was excellent in the ATG-F group (91%), but only 78% in the OKT3 group (P < 0.05) due to a series of rejections that occurred beyond day 100; patient survival (96% and 92%) was similar in both groups. OKT3-treated patients experienced more biopsy-proven rejections (0.6 +/- 0.1/pt.) than ATG-F patients (0.3 +/- 0.1, P < 0.05), and there was a similar, albeit not significant trend in clinical rejections (OKT3: 1.1 +/- 0.2/pt.; ATG-F: 0.8 +/- 0.1/pt.). Infections were more common in the OKT3 group (OKT3: 3.2 +/- 0.3, ATG-F: 2.0 +/- 0.2, P < 0.05), although this was entirely attributable to "minor" infections. On days 1 through 6, CD3 counts were more profoundly depressed with OKT3 therapy. Beyond day 10, however, CD3 counts were lower in the ATG-F group, as were CD2 counts, CD4 counts, and the CD4/CD8 ratio, suggesting a more prolonged immunosuppressive effect of ATG-F. Sensitization occurred more frequently with OKT3 (31%) than with ATG-F (10%), but was usually irrelevant, except in two patients (one in each group), whose grafts were lost because of immunization against OKT3 and ATG-F, respectively. In conclusion, a 7-day induction therapy with OKT3 does not improve outcome or diminish immunological graft loss when compared with ATG-F, but is associated with more rejections, infections, and side effects. ATG-F appears to be preferable for induction immunosuppression after renal transplantation.

Prevention of cancellous bone loss but persistence of renal bone disease despite normal 1,25 vitamin D levels two years after kidney transplantation.

Osteopenia has been observed to occur frequently after renal transplantation. The present study was undertaken to assess whether an immunosuppressive regimen combining cyclosporine with no or the lowest possible maintenance doses of glucocorticoid may prevent osteopenia after kidney transplantation. Thirty-four patients were prospectively followed for two years. Serial blood drawings were done for determination of serum indices of calcium and bone metabolism and an iliac crest bone biopsy was performed at time of transplantation. A second bone biopsy was done in 20 patients during the second year of observation. Creatinine clearance was 56 +/- 6 ml/min one year and 46 +/- 6 ml/min two years after transplantation. Serum parathyroid hormone levels were elevated in 24 patients at time of grafting, decreased significantly thereafter, but remained above the normal range. Ten patients had low or normal serum parathyroid hormone levels at time of transplantation and showed a significant increase after grafting. Two years after transplantation, the mean cumulative dose of prednisone was 5.9 +/- 0.5 g. After the first six months, 30-40% of the patients were not on maintenance doses of steroids. None of the patients experienced fractures, and cancellous bone volume was within or above the normal range in all repeat bone biopsies. It is of note that metabolic bone abnormalities did not resolve 1-2 years after transplantation despite normalization of serum 1,25 vitamin D levels. The histologic abnormalities at the time were consistent with the bone findings in renal failure suggesting resistance of bone to normal circulating levels of 1,25 vitamin D.

Surgical experiences with 191 implanted venous Port-a-Cath systems.

The introduction of totally implantable catheter device has provided a simple, permanent and safe access to the vascular system. They have greatly improved the quality of life of the patients involved, whose activities, daily hygiene and bodily attractiveness remain practically unrestricted. To gain the greatest freedom from complications in the use of fully implantable catheter devices, the following requirements are important in to our experience: 1. Experience with only one kind of catheter system, irrespective of whether it is claimed to be the best, the simplest, or the cheapest. Various companies offer a variety of totally implantable catheter devices. Every system has its advantages and its disadvantages. However, each system also requires a considerable degree of surgical experience and experience in postoperative care and management to keep the complication rate as low as possible. Frequent changing to other systems does not enlarge the experience obtained. 2. The experience of the surgical team. In Basel catheter systems are implanted by three surgeons only. We are convinced that this contributes to our relatively low rate of complications. Brothers et al. (1988) also show that the rate of complications is inversely related to the experience of the surgeon involved. 3. The experience, commitment and training of the nursing staff responsible for the care and maintenance of the implanted catheter device. This care and maintenance of the implanted catheter device should start immediately after the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A and osteonecrosis of the femoral head.

A vascular osteonecrosis has occurred in 5 to 40 per cent of patients who have undergone transplantation of a kidney and generally has been considered to be a complication of the use of corticosteroids. Currently cyclosporin A is in general use for its immunosuppressive property, so that a lower dose of corticosteroids is needed. We analyzed the cases of a series of our patients who underwent transplantation of a kidney in order to find out if our present regimen, using cyclosporin A, influenced the prevalence of osteonecrosis of the femoral head. Of a total of 270 patients, osteonecrosis of the femoral head developed in fifteen of 174 who received conventional immunosuppressive therapy and in only one of ninety-six who received cyclosporin A (p less than 0.05). During the first two months after transplantation, the mean dose of prednisone was approximately 2.5 milligrams per kilogram of body weight per day in the group that received conventional immunosuppressive therapy and approximately 1.1 milligrams per kilogram of body weight per day in the group that received cyclosporin A (p less than 0.001). We concluded that the pathogenesis of the osteonecrosis in patients who underwent transplantation of a kidney was probably related to the higher doses of corticosteroids that were administered.

Risk factors for the development of chronic cyclosporine-nephrotoxicity.

Ninety CSA-treated kidney transplants recipients entered the study. The patients were allocated to three groups based on serum creatinine at 12 months and kidney biopsy findings: control group (serum creatinine less than 177 mumol/l), rejection group (verified by biopsy, serum creatinine greater than 177 mumol/l), nephrotoxicity group (verified by biopsy, serum creatinine greater than 177 mumol/l). Thirty variables were systematically evaluated. The following parameters had a predictive value for the development of chronic CSA-nephrotoxicity: number of CSA-induced episodes of acute deterioration of renal function, CSA trough level (day 0-30, day 31-90), number of unexplained episodes of acute deterioration of renal function, number of nephrotoxic drugs, number of rejection treatments, number of rejection episodes and primary poor renal function. The results indicate that all factors leading to acute renal failure, favor the development of CSA-nephrotoxicity.

Risks and benefits of graft biopsy in renal transplantation under cyclosporin-A.

261 patients who received a kidney transplant under cyclosporin-A immunosuppression were reviewed in order evaluate the benefits and the risks of renal graft biopsies. 240 graft biopsies were performed in 124 of the 261 patients. The biopsy diagnoses were 103x rejection, 90x cyclosporin-A toxicity, 8x acute tubular necrosis, 8x glomerulonephritis, 9x different biopsy results, and 12 cases of normal renal tissue. In 214 cases the clinical course was well explained by the biopsy result. The histological results led to therapeutical changes in 199 cases. 221 of the 240 biopsies were performed without any complications. There was only one biopsy with irreversible and there were 19 biopsies with reversible complications.

von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients.

In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.

Morphologic findings in "zero-hour" biopsies of renal transplants.

The extreme lack of renal grafts for transplantation stimulated us to analyze how strict the selection criteria of kidney donors must be. We investigated therefore if preexisting lesions in renal grafts influence initial and late renal function. 147 zero-hour biopsies of 101 donors (mean age 33, from 6-64 years) were examined. By ligh microscopy 38% of biopsies showed no, 44% showed nonspecific and 18% specific lesions. Nonspecific lesions comprised intimal fibrosis of small arteries in 44%, interstitial fibrosis in 8% and an arteriolar hyalinosis in 29%. Out of 102 immunohistologically examined biopsies 74.5% showed nonspecific IgM/C3 deposits in glomeruli and/or arterioles. An age dependent decrease of normal renal biopsies was found which was most evident in donors older than 40 years. Specific findings consisted of glomerulosclerosis (n = 4), glomerulonephritis (n = 11), intravascular coagulation (n = 10) and eclamptic kidney (n = 1). In case of nonspecific immunohistologic findings and in glomerulonephritis rebiopsies showed that antigen deposits usually disappeared within 4 months. Independent of morphologic findings 82% of transplant recipients had a good initial and late renal function. Since donor age, glomerulosclerosis, glomerulonephritis, intravascular coagulation or eclamptic changes seem not to compromise renal function after transplantation a more liberal choice of donors should be considered.

Long-term benefits and risks of cyclosporin A (sandimmun)--an analysis at 10 years.

To evaluate long-term benefits and risks of CyA therapy in renal transplantation, we analyzed the 10-year experience with all 59 patients who had received a first cadaveric renal graft until August 1983 and were immunosuppressed with CyA. We compared their actual graft survival with that of all 213 patients who had received a first cadaveric graft from 1967 until August 1983, but were immunosuppressed initially with azathioprine and prednisone (AzaP). For comparison of p-creatinine, proteinuria, blood pressure, lipids, uric acid and skin malignancies we evaluated the patients staying unchanged on initial therapy for 10 years (CyA = 12, AzaP = 53). RESULTS. (1) Actual graft survival at 10 years was 34% (20/59) with CyA and 27% (58/213) in AzaP treated patients (intention to treat) (P = .09 = ns). At 1 to 5 years, graft survival was 15% superior with CyA, but after 7 years the survival curve of the CyA-group has closely joined the chronic decline seen in the AzaP group. This behaviour could neither be explained by chronic CyA-nephrotoxicity nor by chronic rejection after switching from CyA to AzaP. (2) P-creatinine at 10 years was significantly (P < .03), but mildly elevated under CyA (130 +/- 52; AzaP = 109 +/- 65). (3) Proteinuria (g/d) at 10 years was not significantly different (CyA = 0.41 +/- 0.58, versus AzaP = 0.83 +/- 1.61). (4) Systolic blood pressure was higher at 10 years under CyA (152 +/- 19) than under AzaP (136 +/-) (P < .02), but diastolic pressure was not (89 +/- 10 versus 84 +/- 12; ns). Antihypertensive drug/patient was twice as high under CyA (1.25 versus 0.64 P < .02). (5) Cholesterol, triglyceride, HDL were not different. 75% of the CyA-patients were steroid free at 10 years, none of the AzaP-patients. (6) P-uric acid was not significantly different in both groups (494 +/- 192 vs 400 +/- 124), but 42% of CyA-patients were on uric acid lowering drug (given after at least one gout attack) as compared to 9% under AzaP (P < .006). (7) Seventeen percent of patients under CyA for 10 years had at least one skin cancer, not different from 15% of AzaP-patients. CONCLUSIONS. The main benefit of CyA was the better graft survival up to 5 years and the chance to stay free of steroids. The main risks of CyA were nephrotoxicity, hypertension and symptomatic hyperuricemia. No difference was found for hyperlipidemia and skin-malignancies.

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.

[Normal kidney function of the transplanted kidney in ipsilateral pelvic artery occlusion 15 years after transplantation. A case report]. / Normale Transplantatnierenfunktion bei ipsilateralem Beckenarterienverschluss 15 Jahre nach Transplantation. Ein Fallbericht.

A case of a 61-year-old women 15 years after right-sided renal transplantation is discussed. She suffered from rest pain in her right leg. Examinations revealed an occlusion of the right common iliac artery without signs of renal dysfunction or severe hypertension. After performing a extraanatomic femoro-femoral crossover bypass the patient had improved leg perfusion without a change in renal function.

[Familial adult cystic kidneys and malignant teratomas after kidney transplantation with cyclosporin therapy]. / Familiäre adulte Zystennieren und maligne Teratome nach Nierentransplantation unter Ciclosporintherapie.

We report on two brothers with adult polycystic kidney disease, malignant teratomas and other genital malformations. Because of the unusual accumulation of malformations of embryologically related organs, we postulate a connection between malformations of the kidneys and the genital tract, on the one hand, and teratomas on the other. No genetic coherence is known so far. It is unlikely that immunosuppression with cyclosporin after transplantation had caused these tumours.

[Problems with long-term immunosuppression following organ transplantation]. / Probleme der Langzeit-Immunsuppression nach Organtransplantation.

Long-term immunosuppression is followed by an increase of malignancies (skin cancer, lymphomas and Kaposi's sarkoma). Among the infectious complications an incidence of bacteraemia up to 48% is found, a relative increase of infection with listeria and salmonella, and viruses from the herpes group. The major side effect of azathioprine is haematologic, whereas Cyclosporin A is nephrotoxic. Three classes of renal functional impairment by Cyclosporine are defined: 1. renal dysfunction, 2. acute nephrotoxicity and 3. chronic nephrotoxicity. Appropriate ways to handle chronic nephrotoxicity are discussed.

[The course of varicose disease. Parallel retrospective study of 2 ethnic groups (Catania-Basel)]. / Curso de la enfermedad varicosa. Estudio retrospectivo en paralelo entre dos diferentes grupos étnicos (Catania-Basilea).

Authors presents a retrospective study with two different ethnic groups, one of them from Catania and the other from Basilea, with varicose veins and subjected to a saphenectomy. They studies the following parameters: age at the entrance, and when varicose veins appeared; correlation between varix appearance date and subjective symptomatology; and rapport between varix complications and its duration. The possible incidence of "ambiental factor" and contrasts between the two groups are considered.