In-vitro growth patterns of bone marrow erythroid progenitors from patients with post-renal transplant erythrocytosis.

BACKGROUND: Erythrocytosis is relatively common after renal transplantation and is associated with a higher risk of thromboembolism. Its aetiology is unclear and there is still debate about the most frequently suggested causes. The culture in vitro of erythroid progenitors is regarded as a useful tool for the differential diagnosis of patients with unclear erythrocytosis. We studied the growth in vitro of bone marrow erythroid progenitors from renal transplant patients with erythrocytosis and controls without erythrocytosis. SUBJECTS AND METHODS: Thirteen renal transplant patients with erythrocytosis and 12 normocythaemic renal transplant controls were studied. The clinical characteristics of these patients were evaluated and serum erythropoietin (Epo) and ferritin levels were determined. Bone marrow erythroid progenitors were cultured both with and without the addition of Epo to the medium. RESULTS: Samples from six polycythaemic patients and seven controls did not grow spontaneously in the absence of exogenous Epo. Three cases of post-transplant erythrocytosis and five controls produced CFU-E, but not BFU-E. A few CFU-E and BFU-E grew spontaneously in samples from four polycythaemic patients but not in samples from the controls. Addition of 1 unit per millilitre Epo caused similar increases in the number of colonies in both polycythaemic patients and controls. Of the nine patients eligible for follow-up, all four with spontaneous growth of BFU-E had transient erythrocytosis and four of the five patients with no spontaneous growth or spontaneous growth of CFU-E only had persistent erythrocytosis requiring treatment with ACE inhibitors. CONCLUSIONS: Pathophysiology of post-transplant erythrocytosis is heterogeneous. In one-third of the patients, there was unexpected, spontaneous and transient growth of BFU-E which was not predictive of permanent erythrocytosis. The results of stem-cell studies suggest that in these cases erythrocytosis may be caused by defective regulation of erythroid progenitor proliferation, possibly due to particular cellular interactions or the effect of cyclosporin on erythropoiesis.

Methodology for using the UMLS as a background knowledge for the description of surgical procedures.

The Unified Medical Language System (UMLS) contains and organizes a large number of terms from a variety of biomedical terminology systems. This study examines the relevance of the UMLS content and structures to the specific purpose of the conceptual representation of medical procedures. The MAOUSSC modelling is a compositional formalism with a description of elementary procedures in terms of elementary concept entities and combinations of such descriptions into more complex ones. The UMLS knowledge base is expected to provide semantically categorized medical concepts and interconcept relations. A method to reuse the UMLS has been developed. Quantitative and qualitative results are presented. Some difficulties in reusing the UMLS as a background knowledge are related to the preeminence of some terminology sources and to the instanciation of interconcept links. Other ones suggest that purpose-independence in categorization cannot be achieved.

Recurrence of immunoglobulin A nephropathy after renal transplantation in the cyclosporine era.

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Schönlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.

IgA nephropathy in patients over 50 years of age: a multicentre, prospective study.

BACKGROUND: IgA nephropathy (IgAN) is considered as a disease of young men under 30 years of age. Findings on clinical and histological presentation and outcome in older patients have rarely been published. METHODS: In a prospective cohort of IgAN patients, recruited over 3 years, 33 patients over age 50 were compared to 96 patients under age 50, according to clinical and histological findings. Actuarial renal survival rate was studied after a mean post-biopsy follow-up of 41 months. RESULTS: Both groups of patients were comparable at baseline for frequency of proteinuria, microscopic haematuria and gross haematuria, but older patients had a significantly higher incidence of hypertension (65 vs 24%, P<0.01). Time between onset and diagnosis of IgAN was similar in both groups. Proteinuria/day, systolic blood pressure, and serum IgA levels were significantly higher, and Ccr was significantly lower in older patients at the time renal biopsy was performed, but serum creatinine and albumin were not. No difference was observed between the two groups for the presence of glomerular or tubulointerstitial lesions. Only endarteritis was significantly more common in older patients (75 vs 34%, P<0.01). End-stage renal failure (ESRF) was confirmed in five patients over 50 and 17 under 50. Renal actuarial survival curves did not show any significant difference between the two groups, even though the six patients who died were classified as ESRF. CONCLUSIONS: When the histological diagnosis of IgAN was established, factors that carry a poor prognosis, i.e. proteinuria, high blood pressure, and decreased Ccr were more commonly present in patients over 50 than under 50. However, after the completion of a relatively short follow-up period, renal survival was identical in the two study groups. Prolonged follow-up is necessary to confirm this trend.

Factors predisposing to post-renal transplant erythrocytosis. A prospective matched-pair control study.

We conducted a prospective study on 81 consecutive patients who had a kidney transplant with graft function for over 3 months to evaluate the prevalence of erythrocytosis following renal transplantation (PTE) and its potential risk factors. True PTE was defined as a RBC mass > 120% of the theoretical value allowing for sex, weight and height. 18 patients (22.2%) developed PTE (RBC mass = 157 +/- 21%) with no evidence of polycythemia vera (PV), or secondary polycythemia due to reduced arterial oxygen, kidney or hepatic tumors. PTE was more common in males (p = 0.041) and less common in patients treated with recombinant erythropoietin (rHEPO) prior to transplantation. 18 non-polycythemic patients (Hb 12.6 +/- 1.3 g/dl) matched for sex, age and renal function were used as case controls. Fewer PTE patients were transfused post-transplantation (p = 0.026). At the time of diagnosis, mean serum EPO was normal and similar to that of controls. PTE patients had lower serum ferritin (p = 0.005) and more commonly received iron supplementation when PTE occurred (p = 0.003). Other clinical factors did not differ significantly between the two groups. Two patients had a thrombotic event, 6 recovered spontaneously and 11 were successfully treated with angiotensin-converting enzyme inhibitors (ACEI). The normalization of Hb, hematocrit and RBC mass in ACEI treated patients was accompanied by a decline in serum EPO (p = 0.008). We conclude that true erythrocytosis is prevalent in cyclosporine-treated renal transplant patients. PTE seems to be an idiopathic erythrocytosis. Pretransplant rHEPO treatment may limit PTE by blunting the increased sensitivity of erythroid precursors to EPO and iron supplementation, which stimulates the development of PTE. ACEI treatment is effective and safe.

Effect of egg consumption in healthy volunteers: influence of yolk, white or whole-egg on gastric emptying and on glycemic and hormonal responses.

The effects of the ingestion of 2 whole eggs (E), 2 egg whites, 2 egg yolks (Y), or no eggs with a standard breakfast on gastric emptying, glycemic and hormonal responses have been studied in 12 healthy young males. E and Y induce a significant delay of gastric emptying, together with reduced blood glucose and insulin peaks (Y). Egg ingestion, whatever the part, increases gastric inhibitory peptide level in blood. Cholecystokinin is enhanced after E or Y ingestion. The results indicate that egg ingestion, especially yolk ingestion, may be of interest in regulating metabolic variables of glucose metabolism.

Risk factors for bacterial infections in chronic haemodialysis adult patients: a multicentre prospective survey.

All adult patients from 13 dialysis centres were prospectively followed up for 6 months in an attempt to appraise the current risk factors for bacterial infections in stable chronically haemodialysed patients. Parameters recorded as potential risk factors for BI were age, gender, cause of renal failure, time elapsed since the start of dialysis, history of transplantation, recent surgical procedure, previous bacterial infection, current immunosuppressive or erythropoietin therapy, type of angioaccess device, and serum ferritin level. Six hundred and seven patients (mean age 56.5 years, range 18-85) were enrolled in the study. Mean time elapsed since the start of dialysis was 4.7 years. One hundred and eighteen patients had developed at least one bacterial infection during the study period whereas 489 had remained free of bacterial infection at the end of the follow-up. In multivariate analysis three parameters were found to be significant and independent risk factors for bacterial infection: previous history of bacterial infection (at least one versus no previous episode), type of angioaccess device (catheter versus native fistula), and elevated serum ferritin level (greater versus lower than 500 micrograms/l). These results support the evidence that impaired host defences in chronic haemodialysis patients may be secondary to the dialysis procedure and suggest that the incidence of bacterial infection in these patients may be further reduced by appropriate supportive therapy.

Knowledge acquisition from the UMLS sources: application to the description of surgical procedures.

The re-usability of lexicons and knowledge in medicine is a crucial challenge. The Unified Medical Language System (UMLS) project has attempted to provide a repository of concepts, semantically categorized for biomedical domain. This paper describes some results about the relevance of UMLS structures for specific purposes. We have focused on the description of surgical procedures. Discussion concerns synonymy of terms, granularity of concepts, and ontology. A preliminary work on the exploitation of interconcept links by a computerized application reveals a heterogeneous implementation of those relationships. However, the UMLS provides a powerful knowledge base for developers.

A system that facilitates the orientation within procedure nomenclatures through a semantic approach.

The representation of medical concepts should provide the flexibility required to support several purposes. We have implemented a model in which medical terms are represented in a standard format based on a semantic description of the terms. We have focused on the description of procedures. Underlying this project is the assumption that information about medical procedures is crucial in the healthcare system. A prototype has been developed for urology. Because of the large number of terms in the Unified Medical Language System (UMLS) and the abundance of links between them, we have experimented in the use of the UMLS as the foundation for our concept base. We assess the usefulness of this approach and discuss its improvements.

Designing a sub-set of the UMLS knowledge base applied to a clinical domain: methods and evaluation.

The UMLS is a complex collection of interconnected biomedical concepts derived from standard nomenclatures. Designing a specific subset of the UMLS knowledge base relevant to a medical domain is a prerequisite for the development of specialized applications based on UMLS. We have developed a method based on the selection of the appropriate terms in original nomenclatures and the capture of a set of UMLS terms that are linked to them in the network to a certain degree. We have experimented it as the foundation for a concept base applied to urology. Results depend on the exhaustiveness of the relationships between the Metal concepts. A preliminary analysis of the sub-base reveals that some adaptations of vocabulary and ontology are required for clinical applications.

Factors associated with low cognitive performance in general practice.

In the preparatory phase of a randomised controlled trial data were collected to assess the magnitude of changes on cognitive functions in 1628 volunteers (age range 45-75 years) that were recruited from general practitioners' patient population. Subjects were administered a short neuropsychological battery of tests including three paper-and-pencil tests, which assessed immediate recall, delayed memory, and attention. Being on antihypertensive medication was associated with low results for all three tests in every age group, and in all strata according to blood pressure levels. Psychotropic drug use was correlated with low results for all three tests. Differences between psychotropic drug users and nonusers increased with age. Antihypertensive treatment and psychotropic drug use seem to be important to consider in longitudinal studies of cognitive decline in aging.

Bacteremia in patients on chronic hemodialysis. A multicenter prospective survey.

A prospective epidemiologic survey of bacterial infections in chronic hemodialysis patients was conducted from September 1, 1989 to February 28, 1990 in 27 dialysis units. Of the 1,455 patients enrolled in the study, 55 presented 63 episodes of bacteremia (incidence of 0.7 bacteremia per 100 patient-months). The portal of entry of sepsis was the vascular access in 50.8% of the episodes. The causative microorganisms were most often gram-positive cocci (69.8%). 23% of the teremic patients had a serum ferritin > 1,000 micrograms/l versus 7% of the nonbacteremic infected patients (p = 0.005). 39.7% of the patients had undergone a surgical operation during the month preceding the bacteremia. Eight patients had a recurrence during the study period and 8 had a metastatic localization: spondylodiscitis 2, septic pulmonary embolus 2, endocarditis 1, arthritis 1, liver abscess 1 and endophthalmia 1. 66% of the episodes required a hospitalization that lasted an average of 20 days. Mortality rate was 6.3%. This prospective study showed a trend towards a reduction in incidence and mortality of bacteremia in patients on chronic hemodialysis.

Dialysis-associated arthropathy: a multicentre survey of 171 patients receiving haemodialysis for over 10 years. The Co-operative Group on Dialysis-associated Arthropathy.

In order to determine the prevalence of dialysis-associated arthropathy (DAA) and what factors favour its development, we conducted a survey in 19 centres in northeastern France, of all patients receiving haemodialysis for over 10 years (171). A diagnosis of DAA was made in 84 patients (49%) by two investigators, using as criteria single or combined presence of carpal tunnel syndrome (32%), erosions and bone cysts of the large limb joints (33%) and destructive spondylarthropathy (14%). The 84 patients with DAA were compared with the 87 dialysis patients free of these clinical or radiological abnormalities. The affected patients were significantly older at the start of dialysis than unaffected patients. The risk of developing carpal tunnel syndrome increased with the duration of dialysis. Amyloid deposits were found in carpal tunnel tissue obtained from 24 of the 39 operated patients (62%) during surgery. Destructive spondylarthropathy was significantly associated with the presence of disc calcifications and more frequent in AN 69-treated patients in whom secondary hyperparathyroidism appeared to be more severe. The use of an AN 69 membrane for at least 90% of the dialysis period (in 15 patients) was not associated with a lower prevalence of DAA. We found that after 10 years of haemodialysis DAA occurred whatever type of membrane was used and the prevalence increased with the patient's age and the duration of dialysis.

[Expiratory capnography in asthma. Perspectives in the use and monitoring in children]. / La capnographie expiratoire dans l'asthme. Perspectives d'utilisation chez l'enfant et comme méthode de monitorage.

The shape of the capnogram, which is related to uneven ventilation, is modified in obstructive diseases and especially during crisis of asthma. The most significant change is a rise in the slope of the "alveolar plateau". In this study, we measured the end-tidal slope (ETS) of the capnogram, calculated on 0.36 s before the end of expiration, and we compared this indice to usual spirometric measurements (FEV 1) in 21 control subjects and in 24 asthmatic subjects. The mean ETS in control subject was 0.08 +/- 0.06%/s, it was 0.3 +/- 0.23% in asthmatic subjects (p < 0.001). In the latter, we found a very significant correlation between ETS and FEV 1 (r = 0.83, p < 0.001). Thirteen asthmatic subjects were tested for a second time, immediately after inhalation of a beta 2-mimetic drug. They exhibit a very strong correlation between the rise of FEV 1 and the loss of ETS (r = 0.96, p < 0.001). These results show that the analysis of the capnogram's shape is a quantitative method for evaluating the severity of the bronchospasm. This ability, added to specific advantages (non-invasiveness, effort-independence) opens new fields of application to capnography: measurement of the bronchospasm in children, computerized monitoring of asthma.

[Urinary tract infections during the 1st month after kidney transplantation]. / Infections urinaires du premier mois post-transplantation rénale.

The incidence and the predisposal factors of urinary tract infections (UTI) in the first month post-transplant were studied in 255 kidney transplantations (252 patients). UTI episodes were demonstrated in 73.7% of the grafts. The most common organisms were: Escherichia coli (35.8%), Staphylococcus (33.6%), Streptococcus D (11.2%), Klebsiella (5.3%). The infectious episodes were recurrent in 39% of the cases. The majority of the UTIs were asymptomatic but 7% of the infections led to septicaemia. Etiology of end-stage renal disease, pre-graft binephrectomy, asymptomatic vesicoureteral reflux into the patient's own kidneys, type of immunosuppressive treatment, acute tubular necrosis, rejection episodes, urological complications, coexistent other infections were not predisposal factors. Bacteriuria was more frequent in female than in male patients. The incidence of UTI was found to be statistically increased with history of UTI preoperatively (p = 0.039) and the use of ureteral catheter (p = 0.018). Occurrence of UTI was less common when the donor was treated by antibiotics before brain death (p-0.025). These results provide additional support for regular monitoring of urine cultures in the first month post-transplant. They should help to identify means of reduction of this infectious risk.

Evaluation of a screening test for detecting urinary tract infection in newborns and infants.

The results of a study of a screening test for urinary tract infection (UTI) in infants under 18 months is reported. Two hundred and forty three urine specimens were tested in the laboratory using AMES Multistix 8SG reagent strips read by photometer. The strips included three potential markers for urinary tract infection: leucocyte esterase, nitrite, and protein. The predictive value of a positive result (PPV) was low. The predictive value of negative test (NPV) when combining the screen of leucocyte esterase, nitrite, and protein was 99.4% with no difference between boys and girls. The test for leucocyte esterase had a 97.6% negative predictive value. An examination of the results by age confirms the good NPV in all age groups. Paediatricians should find Multistix 8SG strips a useful aid in the diagnosis of urinary tract infection in infants, and that costly culture of samples with negative strip tests can be avoided.