Immunologic monitoring and aspergillosis in renal transplant patients

Three cases of pulmonary aspergillosis in a "high risk" population of renal transplant recipients are presented. The source of infection was traced to the forced air exhaust system of the Transplantation Unit. Early definitive diagnosis of the infection was very important for effective management. Immunologic monitoring was demonstrated to be instrumental in indicating the early presence of infection, and as a guideline to reduced immunosuppression during therapy. Bronchoscopy with brushings and endobronchial cavitary biopsy were valuable methods for obtaining the infected tissue. Amphotericin B was effective when therapy was started early. Adequate levels of the drug were obtained by varying the dose and frequency of administration according to serum inhibitory titers. Control of infection was aided by immunologic monitoring at regular intervals.     

Future trends in renal replacement therapy

The authors report a case about relapsing corneal ulceration in a patient with rheumatoid arthritis. Treatment of such perforated and preperforated corneal ulcers is a difficult task. The poor visual outcome of an emergency penetrating keratoplasty leads to the use of other methods (conjunctival flaps, corneal graft, keratopatch, tissue adhesive). This case report stresses the importance of preserving the anatomy of the eye allowing in a record time the performance of corneal graft. The use of immunosuppressive drugs is also discussed because of the existence of a rheumatoid arthritis with eye involvement.     

Future trends in substance abuse.

Argues that as illicit drugs with increased abuse liability come into vogue, a broader segment of the population will be at risk for becoming addicted. Consequently, the attendant effects of abuse, including acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection, will grow proportionately. Health care providers will need to become more astute and creative to provide effective rehabilitation for addicted individuals. (0 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New trends in ECG Holter monitoring

The authors review contemporary possibilities of Holter ECG monitoring. In the first group of patients they emphasize possibilities and the yield of long-term ambulatory ECG monitoring by means of an apparatus started by the patient. The second group of patients was examined by Holter monitoring, using an oesophageal lead. It is a method hitherto not used in the Czech Republic, which if properly indicated, improves the non-invasive diagnosis of cardiac arrhythmias.     

Future trends for experimental surgery in laboratory animal science

It has been suggested that all children with skull fractures require urgent CT scanning to exclude intracranial injury. Adhering to such a policy could both tax limited scanning facilities and result in unnecessary exposure to radiation. The aim of this study is to assess the level of consciousness in determining the need for urgent CT scanning, and the possible role of the mechanism of injury as a secondary risk factor. We identified 140 children admitted during a 7-year period with a skull fracture after falling outside the home. Thirteen children had a diminished level of consciousness. Scans were performed in nine, and seven of the scans revealed significant intracranial injuries. By comparison, all 127 children with a normal level of consciousness recovered fully. Scanning was performed in only eight of them; seven scans were normal and one revealed a small subarachnoid heamorrhage which did not require active treatment. In addition, all 13 children with a diminished level of consciousness had sustained their injuries by falling from greater than their own standing height. By comparison, none of the children who had sustained their skull fractures by tripping up had a diminished level of consciousness or a significant intracranial injury. We conclude that all children with a diminished level of consciousness need to undergo an urgent CT scan. Children with skull fractures and a normal conscious level may be managed initially by neuroobservations and the clinician may be further reassured if the child's injury resulted from tripping up.     

Rhabdomyolysis in transplant patients

In a retrospective analysis of all our patients with seizure onset prior to age 16 years, 25 patients with primary generalized tonic (n = 10) or tonic-clonic (n = 15) seizures were identified. These patients constituted 5.7% of the total seizure patient population in our institute between the ages of 1 month and 16 years. The natural history of generalized tonic-clonic seizures is known to be benign; however, that of isolated primary generalized tonic seizures is not clear. Therefore, an attempt was made to characterize the patients suffering from primary generalized tonic seizures and determine their outcome. Analysis of our patient population shows that both seizure types are characterized by early onset of generalized seizures that appear in normally developed children with a normal electroencephalographic background. The children usually respond quickly to antiepileptic drugs. A long-term follow-up (mean period of 7.6 years) was possible in 84% of the patients, and showed that 95% of them were seizure free at the end of the follow-up period. There was no significant difference between the two groups in regard to age of onset, family history, and seizures at follow-up. In conclusion, the natural history of patients with generalized tonic seizures is similar to the benign course of those with generalized tonic-clonic seizures.     

Clinical and immunological characteristics of transplant recipients with recurrent acute rejection episodes

Diet may play a key role in the pathogenesis of cancer and evidence for the role of a reduced intake of micronutrients with antioxidant properties have been increasingly reported. Until now, epidemiologic research in humans has focused on the negative effect of different diets containing excessive caloric intake and relatively little is known on the possible correlation between slimming diets and the incidence of acute leukemia. In this report we describe the temporal association of imbalanced slimming regimens and the subsequent diagnosis of acute leukemia in three cases. This association may be coincidental or perhaps suggests a possible relationship of the diet with the development or progression of acute leukemia.     

Hyperlipidaemia in renal transplant patients

OBJECTIVES: The aim of study was to assess the prevalence and severity of hyperlipidaemia in renal transplant patients in a Nordic country. DESIGN: Multicentre, cross-sectional study. SETTING: Outpatients and ward inpatients registered from 23 hospitals covering all regions of the country. SUBJECTS: Renal transplant patients with a functioning graft were registered: 406 patients in all; that is, 43% of the national renal transplant population. All patients used prednisolone, 71% used cyclosporine, either with (51%) or without (20%) azathioprine. Total cholesterol values from general population were obtained from a national survey. MAIN OUTCOME MEASURES: Blood lipids and their relation to clinical parameters. RESULTS: Total cholesterol was significantly higher in transplant patients than in the general population for both genders and all age groups (P < 0.01). Female patients had higher total cholesterol (mean +/- SD: 7.49 +/- 1.61 mmol L(-1)) than males (7.01 +/- 1.55 mmol L(-1); P < 0.001), and also higher HDL cholesterol (1.55 +/- 0.43 vs. males: 1.32 +/- 0.46 mmol L(-1); P < 0.001). Triglycerides were equally elevated in both genders, and 33% had values above 2.2 mmol L(-1). Reduced creatinine clearance, a high body-mass index, female gender, hypertension, and coronary artery disease were independently associated with higher total cholesterol. Beta blockers were associated with lower HDL cholesterol and higher triglycerides, and diuretics with higher triglycerides. Blood lipid levels were not associated with cyclosporine immunosuppression. CONCLUSION: Hyperlipidaemia is prevalent after renal transplantation, and is associated with impaired graft function, hypertension, and with the use of beta blockers and diuretics, but not with the use of cyclosporine.     

Tuberculosis in liver transplant patients

Beta human chorionic gonadotrophin levels have been assessed in blood serum of 79 patients with bladder tumours before and seven days after transurethral electroresection (TUR). With the growth grade of anaplasia and staging the mean serum beta HCG level increased. Beta HCG was a good biological marker to differentiate between superficial and deep tumours.     

Ano-genital neoplasia in renal transplant patients

Ano-genital neoplasia is about 20 x more common in renal transplant patients than the general population. Neoplasms in the immunosuppressed are more morbid and mortal because: patients are younger; tumors are more undifferentiated; they have more and larger foci; more sites are involved; neoplasms tend to persist, recur and progress; and there are more complications from treatments. Intraepithelial neoplasia engenders some morbidity. Invasion is rarer, but when it occurs, it is always morbid, and all too often mortal. Invasive ano-genital cancer is primarily preventable because the lower genital and anal tracts are accessible to inspection, cytologic screening, endoscopy and biopsy. Prime prevention is avoiding infection with the Human Papilloma Virus (HPV). Next best is detecting HPV/intraepithelial neoplasia early with frequent inspection, cytology and liberal biopsies; and then removing any condylomas or intraepithelial neoplasia that develop.     

New trends in biological monitoring: application of biomarkers to genetic ecotoxicology

We extended observations on cocaine-induced turning and its interactions with mu-opioid receptor agonists in nigrally-lesioned rats to GBR12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenyl-propyl]-piperazine) , a selective dopamine reuptake inhibitor. GBR12909 produced turning that was potentiated by the mu-opioid receptor agonists morphine and methadone. The effects of these opioids were blocked by the general opioid receptor antagonist naloxone, which did not affect the action of GBR12909. The reuptake inhibitors nisoxetine (norepinephrine) and fluoxetine (serotonin) did not produce turning alone or in combination with morphine. Antagonists selective for each opioid receptor subtype did not alter GBR12909-induced turning. However, naltrexone, another general opioid receptor antagonist, potentiated turning induced by GBR12909. This was blocked by naloxone, suggesting that naltrexone has opioid receptor agonist actions, in contrast to naloxone. These results indicate that cocaine-induced turning and its potentiation by mu-opioid receptor agonists are dependent upon the inhibition of dopamine reuptake.     

Population pharmacokinetics of sirolimus in kidney transplant patients

OBJECTIVE: To characterize the dose-related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two-stage and nonlinear mixed-effect model population methods. METHODS: Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady-state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first-order absorption (ka) and a lag-time. RESULTS: The nonlinear mixed-effect model method (P-Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration-independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half-life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag-time of 0.27 hour (35.1%), and ka of 2.77 hr-1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interactions. CONCLUSION: This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.