Adult heart transplantation under tacrolimus (FK506) immunosuppression: histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction

BACKGROUND: Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. METHODS: We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. RESULTS: In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat refractory rejection in three patients from the CLI-treated arm. Concern has been raised in the literature about the possibility of tacrolimus being a direct hepatotoxin and an accelerant of allograft obliterative arteriopathy. However, no evidence to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this regard. CONCLUSIONS: Tacrolimus is an effective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus immunosuppression does not significantly differ from those given conventional, cyclosporine-based triple therapy with lympholytic induction.     

Magnocellular and parvocellular visual pathways are both affected in a macaque monkey model of glaucoma

OBJECTIVE: To review the literature addressing the use of the pulmonary artery catheter (PAC) in patients with respiratory failure. DATA SOURCE: All pertinent English language articles dealing with pulmonary artery catheterization in patients with respiratory failure were retrieved from 1983 through 1996. STUDY SELECTION: Articles were chosen for review if the use of pulmonary artery catheterization in patients with respiratory failure was studied or reviewed. DATA EXTRACTION: From the articles selected, information was obtained about changes in therapy and changes in outcome associated with PAC use in patients with respiratory failure. DATA SYNTHESIS: Evidence exists to suggest that use of the PAC in patients with respiratory failure often results in a change in diagnosis and therapy. Inadequate evidence exists to accurately determine benefit or harm from PAC use in patients with respiratory failure. CONCLUSION: The optimal role of the PAC as a diagnostic and monitoring device in different types of respiratory failure has not been clearly defined. Research is needed to determine the role of the PAC in very carefully defined groups of patients with respiratory failure.     

Patellar enthesopathy in childhood: a new clinical and radiographic observation

Enthesitis occurs commonly in patients with seronegative spondyloarthropathies. The patella is frequently affected by enthesopathy, but overgrowth has not been reported as a manifestation of enthesitis in pediatrics. We describe 3 patients with seronegative enthesopathy and arthropathy syndrome and patellar overgrowth.     

The basis of surgical treatment for extensive postoperative abdominal hernia

The hernioplasty method was elaborated by the authors. The method stipulates the prosthesis of polyurethane placement in the duplicature from the hernial sac and parietal peritoneum and is sewn under the hernial defect edge, which are then sewn contactly. With the application of method elaborated 36 patients were operated on, suffering from large abdominal hernia. In 2 patients the lymphorhagia was observed in postoperative period during 9 days, in 1 the wound have suppurated and the prosthesis was removed. The late follow-up results were observed from 3 months till 3 years, the hernia recurrence was not revealed.     

Intensive care 1980-1995: change in patient characteristics, nursing workload and outcome

OBJECTIVE: To assess temporal changes in patient characteristics, nursing workload and outcome of the patients and to compare the actual amount of available nursing staff with the estimated needs in a medical-surgical ICU. DESIGN: Retrospective analysis of prospectively collected data. SETTING: A medical-surgical adult intensive care unit (ICU) in a Swiss university hospital. PATIENTS: Data of all patients staying in the ICU between January 1980 and December 1995 were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The estimated number of nurses needed was defined according to the Swiss Society of Intensive Care Medicine (SGI) grading system: category I = one nurse/patient/shift (= 8 h), category II = one nurse/two patients/shift, category III = one nurse/three patients/shift. An intervention score (IS) was obtained, based on a number of specific activities in the ICU. There was a total of 35,327 patients (32% medical and 68% postoperative/trauma patients). Over time, the number of patients per year increased (1980/1995: 1,825/2,305, p < 0.001) and the length of ICU stay (LOS) decreased (4.1/3.8 days, p < 0.013). There was an increase in the number of patients aged > 70 years (19%/28%, p < 0.001), and a decrease in the number of patients < 60 years (58%/41%, p < 0.001). During the same time period, the IS increased two-fold. Measurement of nursing workload showed an increase over time. The number of nursing days per year increased (1980/1995: 7454/8681, p < 0.019), as did the relative amount of patients in category I (49%/71%, p < 0.001), whereas the portion of patients in category II (41%/28%, p < 0.019) and category III (10%/0%) decreased. During the same time period, mortality at ICU discharge decreased (9.0%/7.0%, p < 0.002). CONCLUSIONS: During the last 16 years, there has been a marked increase in workload at this medical-surgical ICU. Despite an increase in the number of severely sick patients (as defined by the nursing grading system) and patient age, ICU mortality and LOS declined from 1980 to 1995. This may be ascribed to improved patient treatment or care. Whether an increasingly liberal discharge policy (transfer to newly opened intermediate care units, transfer of patients expected to die to the ward) or a more rigorous triage (denying admission to patients with a very poor prognosis) are confounding factors cannot be answered by this investigation. The present data provide support for the tenet that there is a trend toward more complex therapies in increasingly older patients in tertiary care ICUs. Calculations for the number or nurses needed in an ICU should take into acount the increased turnover of patients and the changing patient characteristics.     

Phytotoxicity and cytotoxicity of the fumonisin C and P series of mycotoxins from Fusarium spp. fungi

Fumonisin C (FC) and P (FP) are two recently identified series of sphingosine-analog mycotoxins, for which biological activities have not previously been reported. FC1, FC2 and OH-FC1 (1 microM) exhibited strong phytotoxicity comparable to the standard FB1 in duckweed (Lemna pausicotata L.) cultures, whereas FC3 and FC4 were moderately phytotoxic. Conversely, FP1 exhibited weak phytotoxicity only at higher concentrations (> or =10 microM). These mycotoxins exhibited a similar pattern of cytotoxicity with FB1-sensitive cultured mammalian cell lines, H4TG and MDCK.     

Bacteremia and fungemia in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan

To understand the etiology and clinical outcome of bacterial and fungal sepsis in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan, we conducted a prospective study of nonmycobacterial bacteremia and fungemia in HIV-infected patients with fever who were admitted to a university hospital in Taiwan during a 42-month period. Of 210 patients, 41 (19.5%) had a total of 52 episodes of sepsis due to nonmycobacterial bacteria or fungi, or both (15.5% of 336 episodes of fever). All but one patient had acquired immunodeficiency syndrome (AIDS), and the mean CD4 lymphocyte count was 29/microL (range, 0-321/microL). A total of 57 pathogens (39 bacteria and 18 fungi) were isolated from blood; polymicrobial sepsis due to both bacteria and fungi occurred in four episodes. Nontyphoid Salmonella (NTS) was the most common cause of community-acquired bacteremia (24/30, 80%). Staphylococcus aureus bacteremia was diagnosed in three episodes while Streptococcus pneumoniae bacteremia was found in only one. Cryptococcus neoformans was the most common cause of fungemia and was responsible for 12 episodes, while fungemia due to Penicillium marneffei and Histoplasma capsulatum, two emerging fungi in Taiwan, were diagnosed in four cases and one case, respectively. Nine episodes, eight of bacteremia and one of candidemia, were nosocomial. The overall in-hospital mortality was 29%, and nosocomial sepsis was associated with a higher mortality rate (56%, p = 0.02). The mean duration of survival after recovery from initial sepsis was 426 days. We conclude that NTS bacteremia was the most common cause of sepsis in patients with advanced HIV infection in Taiwan and clinicians caring for such patients should watch for emerging fungal infections. Nosocomial sepsis was associated with a high mortality rate. The mean survival duration after recovery from sepsis of our patients was short.     

A mathematical model of the dynamics of scrapie in a sheep flock

A mathematical model is developed for the dynamics of an outbreak of scrapie in a single sheep flock with the aim of assisting the interpretation of field data. The model incorporates age structure of the sheep population, both horizontal and vertical transmission, genetic predisposition to infection, variable initial load of the infectious agent, and increasing infection load during an incubation period of the same order as sheep life expectancy. This leads to system of partial differential equations with respect to time, age and infection load. Numerical analyses using this model demonstrate that a scrapie outbreak is likely to be of long duration (several decades), will lead to reduction of scrapie susceptible allele frequency (but not to zero), and has different dynamics in homozygous and heterozygous susceptible sheep, even if these genotypes are equally susceptible, due to the different contributions of vertical infection to transmission to genotypes.