Effects of changing immunosuppressive regimen on the incidence, duration, and viral load of cytomegalovirus infection in renal transplantation: a single center report

Abstract: Background. In this retrospective single center study we have evaluated the relation between the immunosuppressive regimen and the incidence and characteristics of cytomegalovirus (CMV) infection in the setting without CMV prophylaxis from 1989 through 1998. Methods. All (470) first cadaveric renal transplantations in nonsensitized (PRA < 60%) patients were analyzed. Immunosuppression consisted of cyclosporine A (Sandimmune) and prednisolone from 1989 through 2-1993 (S; 189 patients), of cyclosporine microemulsion (Neoral) and prednisolone from 3-1993 through 5-1997 (N; 200 patients) and of mycophenolate mofetil, Neoral and prednisolone from 5-1997 until 1998 (M; 81 patients). The CMV pp65-antigenemia was measured routinely at least once weekly from day 10 till 12 weeks after transplantation or until pp65-antigenemia became negative. No CMV-prophylaxis was given. Results. By changing from Sandimmune to Neoral and by adding mycophenolate mofetil, respectively, we observed a higher frequency of especially secondary CMV infections (S vs. N vs. M, respectively, 28 vs. 50 vs. 63%, P  = 0.026; S vs. N, P  = 0.027; S vs. M, P  = 0.015; and N vs. M, n.s). The CMV infections lasted longer (median duration antigenemia S vs. N vs. M, respectively, 3 vs. 5 vs. 7 weeks, P  = 0.0003; S vs. N, P  < 0.002; S vs. M, P  < 0.001; and N vs. M, P  < 0.05). Viral load was higher in M (median maximal pp65-antigenemia S vs. N vs. M, respectively, 19 vs. 14.5 vs. 73, P  < 0.01; S vs. N, n.s.; S vs. M, P  < 0.001 and N vs. M, P  < 0.01). Conclusions. The use of Neoral and the addition of mycophenolate mofetil caused significant changes in the incidence, duration and viral load of CMV infections.     

A case of tuberculous pericarditis developing constrictive pericarditis

A case of constrictive pericarditis which developed after the onset of clinical manifestation of tuberculous pericarditis was reported. A 75-year-old male, complaining of anorexia, was admitted to our hospital. Adenosinedeaminase (ADA) level in pericardial effusion was found to be increased, and the culture of pericardial effusion was positive for tubercle bacilli. Diagnosed as having tuberculous pleuritis and pericarditis, he underwent chemotherapy for tuberculosis. However, massive pleural effusion developed later and pleural effusion drainage was carried out. Despite repeated drainage, pleural effusion continued to recur. Chest CT revealed apparent pericardial thickening, in addition, cardiac catheterization revealed elevation of mean right atrial pressure and marked deterioration of cardiac functions including decrease of cardiac output. These findings were compatible with constrictive pericarditis. After these investigations a diagnosis of constrictive pericarditis was established, and the patient underwent a pericardiectomy. Pathological examination of resected specimens revealed tuberculous inflammation.     

Development of web-based diabetic patient management system using short message service (SMS)

We developed a blood glucose management system using the Internet and short message service (SMS) which can lessen the social economic burden and materialize an individualized diabetes mellitus management. A total of 185 diabetic patients participated in this study and their mean age was 42.4 years old (8-79 year-old). Participants sent their self-measured blood glucose levels, medication and its dosages, amount of meal, and degree of exercise to their health providers in this specialized web-based diabetes management system for 3 months. The health providers consisting of endocrinology specialists, dietitians, and nurses sent recommendations for individualized diabetes management according to the data on the web. Laboratory tests including lipid profiles and glycated hemoglobin (HbA1c), and a survey of satisfaction about this system were performed before and after the study period. The mean HbA1c improved from 7.5 +/- 1.5 to 7.0 +/- 1.1% after using the management program (P = 0.003). The mean serum triglyceride and HDL-cholesterol levels turned for the better also. HbA1c improved from 8.4 +/- 1.2 to 7.5 +/- 1.0% after applying this program to patients with the HbA1c of 7% or higher at baseline (P = 0.010). We propose this web-based diabetic patient management system as a new tool for communication between health care providers and patients.     

Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.     

General Internists' Perspectives Regarding Primary Care and Currently Related Issues in Korea

Although primary care has been recognized as an essential element of the healthcare system, the primary healthcare of Korea has not been highly valued. Listening to the voices of physicians who are engaged in primary care should be the first step for improving the level of primary care in Korea. In this study, we conducted a questionnaire survey of general internists to investigate their perspectives regarding primary care, and which included the evaluation of current primary care, perception of the five, key attributes of primary care, and their opinions regarding the management system of chronic diseases. A total of 466 general internists'' responses were used in this analysis. The results showed that primary care is considered to have an important role, according to general internists, although their evaluation of the overall status of primary care in Korea indicated that it is poor. The respondents also indicated that the functions of coordination and comprehensiveness in primary care, which can be integral for treating patients with chronic diseases, are most vulnerable. Given the high level of agreement regarding the need for a new medical management system for chronic diseases, based on physicians'' autonomy and provided by clinics, establishing a policy encouraging the participation of general internists should be emphasized.

Graphical Abstract

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Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus

Pharmacological studies have suggested that long-term potentiation (LTP) and long-term depression (LTD) and depotentiation, three forms of synaptic plasticity in the hippocampus, require the activity of the phosphatase calcineurin. At least two different isoforms of calcineurin are found in the central nervous system. To investigate whether all of these forms of synaptic plasticity require the same isoforms of calcineurin, we have examined LTD, depotentiation, and LTP in mice lacking the predominant calcineurin isoform in the central nervous system, Aalpha-/- mice. Depotentiation was abolished completely whereas neither LTD nor LTP were affected. These studies provide genetic evidence that the Aalpha isoform of calcineurin is important for the reversal of LTP in the hippocampus and indicate that depotentiation and LTD operate through somewhat different molecular mechanisms.