Pet ownership increases human risk of encountering ticks.

We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products.

Deaths within 90 days from starting renal replacement therapy in the ERA-EDTA Registry between 1990 and 1992.

BACKGROUND: Patients who die within 90 days of commencing renal replacement therapy (RRT) may be recorded by some centres and not others, and hence data on mortality and survival may not be comparable. However, it is essential to compare like with like when analysing differences between modalities, centres and registries. It was decided, therefore, to look at the incidence of deaths within 90 days in the ERA-EDTA Registry, and to try to define the characteristics of this group of patients. METHODS: Between 1 January 1990 and 31 December 1992, 78 534 new patients started RRT in 28 countries affiliated to the ERA-EDTA Registry. Their mean age was 54 years and 31% were over 65 years old. Eighty-two per cent of the patients received haemodialysis (HD), 16% peritoneal dialysis (PD) and 2% had preemptive transplantation as first mode of treatment. RESULTS: From January 1990 to March 1993 the overall incidence of deaths was 19% and 4% of all patients died within 90 days from the start of RRT. Among those dying within 90 days 59% were over 65 years compared to 53% over 65 years in those dying beyond this time (P<0.0001). The modality of RRT did not influence the distribution of deaths before and after 90 days. Vascular causes and malignancy were more common in those dying after 90 days, while there were more cardiac and social causes among the early deaths. Mortality from social causes was twice as common in the elderly, who had a significantly higher chance of dying from social causes within 90 days compared to those aged under 65 years. The overall incidence of deaths within 90 days was 3.9% but there was a wide variation between countries, from 1.8% to 11.4%. Finally, patient survival at 2 years was markedly influenced in different age groups when deaths within 90 days were taken into account. CONCLUSIONS: The incidence of deaths within 90 days from the start of RRT was 3.9%, with a marked variation between countries ranging from 1.8% to 11.4%, which probably reflects mainly differences in reporting these deaths, although variable selection criteria for RRT may contribute. Deaths within 90 days were significantly more frequent in elderly patients with more early deaths resulting from cardiac and social causes, while vascular causes of death and malignancy were more common in those dying after 90 days. Patient survival analyses should take into account deaths within 90 days from the start of RRT, particularly when comparing results between modalities, countries and registries.

Progelatinase A is produced and activated by rat hepatic stellate cells and promotes their proliferation.

Activated hepatic stellate cells (HSCs) are a potential source of gelatinase A, which accumulates in fibrotic livers. Progelatinase A activation requires its binding to a complex of membrane-type matrix metalloproteinase (MT-MMP) and tissue inhibitor of metalloproteinases (TIMP)-2. These studies examine gelatinase A, MT1-MMP, and TIMP-2 synthesis by HSCs during activation in vitro and the potential role of gelatinase A in promoting HSC proliferation. Gelatinase A, MT1-MMP, and TIMP-2 messenger RNA (mRNA) were all upregulated in HSCs activated on plastic over 5 to 14 days. Gelatinase A expression was maximal at 7 days of culture, coinciding with the peak of HSC proliferation and the onset of procollagen I and alpha-smooth muscle actin (alpha-SMA) mRNA expression. Active forms of gelatinase A of 62 kd and 66 kd were secreted by activated HSCs and reached a maximum of 12.1% of total enzyme in 14-day culture supernatants. Treatment of HSCs with concanavalin A (con A) induced activation of MT1-MMP and enhanced secretion of activated gelatinase A, which reached a maximum of 44.4% of the total enzyme secreted into culture supernatants using 30 microgram/mL con A. [(14)C]-gelatin degradation assays confirmed the presence of gelatinolytic activity in activated HSC supernatants, which reached a maximum level at 7 days of culture. Antisense oligonucleotide inhibition of endogenous progelatinase A production, or the MMP inhibitor 1,10-phenanthroline inhibited (3)H-thymidine incorporation into HSC DNA by greater than 50%. We conclude that HSCs produce progelatinase A during activation in vitro and activate this enzyme coincident with MT1-MMP and TIMP-2 synthesis. Gelatinase A activity is required for maximal proliferation of HSCs in vitro suggesting this metalloproteinase is an autocrine proliferation factor for HSCs.

Hypertension as cause of end-stage renal disease: lessons from international registries.

The incidence of hypertension as cause of ESRD has doubled in the ERA-EDTA Registry in the past two decades, going from 7 to 13%. It is very possible that this is not a real increase in the incidence of hypertension as cause of ESRD, but rather a consequence of greater acceptance of older patients, a phenomenon that has simultaneously occurred. There are geographic differences in the incidence of hypertension as cause of ESRD, from 6% in Japan to 28.5% in the U.S., and 13% in Europe. With the present data, it is impossible to know if these differences are real. The diagnostic criteria used are not uniform and a consensus would be necessary to establish uniform diagnostic criteria for nephrosclerosis or ischemic nephropathy. The percentage of patients starting renal replacement therapy (RRT) with unknown primary renal disease is very different in the U.S. and Europe. This could be a critical factor in explaining these differences. Survival of patients at 5 and 10 years with renal vascular disease did not improve from 1977 to 1989. The same occurs with survival of patients with standard primary renal disease, although this is better than that of patients with renal vascular disease. To interpret this lack of improvement in survival of patients over a decade, we must take into account that at the same time there has been a significant increase in the age of patients starting RRT. Therefore, when the population of patients of under 55 is analyzed, there is evidence that those starting treatment in the 80's have much better survival than those starting in the 70's. However, survival of patients with renal vascular disease continues to be poorer than that of patients with standard primary renal disease. This lower survival of patients with renal vascular disease seems to be related to higher cardiac mortality, which is in alignment with the diagnosis of hypertension as cause of renal failure.

How physicians can prevent medication errors: practical strategies.

To eliminate and reduce medication errors, health care organizations must develop a consistent approach that allows examination of errors in a supportive atmosphere with a bias toward preventing future errors rather than punishing past ones. Until improved systems are in place, physicians can help prevent many of the most serious medication errors by observing some basic safety practices, such as writing orders whenever possible and limiting verbal orders to urgent or emergency situations, writing clearly and neatly, and avoiding abbreviations.

Transplantation Report. 2: Pre-emptive renal transplantation in adults aged over 15 years. The EDTA-ERA Registry. European Dialysis and Transplant Association-European Renal Association.

Between 1985 to 1992, 2545 renal transplantation (RTx) were performed as pre-emptive grafts in adults. This procedure represented 7.2% of first RTx for patients starting first renal replacement therapy (RRT) during this period, 6.1% of RTx performed in 1992 and 5.6% of all RTx ever performed and reported to the EDTA Registry. The procedure is more frequent in cases of live donor grafts, representing one third of pre-emptive RTx. Both 5 year patient and graft survivals are unaffected by dialysis duration prior to the first RTx: none in pre-emptive, < 1 years, 1-5 years or > 5 years. In our personal view, this procedure should be developed.

Report on management of renale failure in Europe, XXVI, 1995. Rare diseases in renal replacement therapy in the ERA-EDTA Registry.

The proportion of centres returning the ERA-EDTA Registry questionnaires has decreased considerably in recent years. Demographic information, based on the response rate of centres in 1994 (44%), does not allow reasonable projections for management of renal failure in Europe. To encourage the participation of non-responding centres, the timing was right to show the powerful impact of the ERA-EDTA Registry as a supra-national registry, by studying patients in renal replacement therapy (RRT) suffering from rare diseases. Four such diseases, Fabry's disease, nephropathy due to cyclosporin (CsA), nephropathy due to cisplatin and scleroderma, were studied using the records of 440665 patients on file up to 31 December 1993. There were 83 patients with Fabry's disease (0.0188%), 85 patients with CsA nephropathy (0.0193%), 120 patients with cisplatin nephropathy (0.0272%) and 625 patients with scleroderma (0.142%). Scleroderma was introduced as a primary renal disease (PRD) in the ERA-EDTA Registry in 1977. Seven patients were accepted for RRT in that year, whereas the number increased to over 50 new patients per year after 1986. More than half of the patients were aged over 55 years, and 68% of them were women. Survival rate of dialysis patients suffering from scleroderma was 22% at 5 years, compared to 51% in patients with standard primary renal diseases. The main causes of death were cardiovascular complications (41%), cachexia (15%) and infection (10%). Survival of first graft in a small number of 28 patients was 44% at 3 years, compared to 60% in standard PRD. Patient survival after first transplant, however, was higher by 32% at 3 years compared to that of dialysis patients. Cisplatin nephropathy was introduced as a PRD in the ERA-EDTA Registry in 1985, and since then six to 19 new patients have been accepted for RRT each year. The main reason for undergoing cisplatin treatment was ovarian (32%) and testicular cancer (21%), and the mean interval from treatment to RRT was 21.5 months, ranging widely from 0.1 to 131 months. Patient survival on dialysis was 22% at 5 years, compared to 51% in patients with standard PRD. Malignancy and cachexia accounted for over 60% of the total number of deaths. CsA nephropathy was introduced as a PRD in the ERA-EDTA Registry in 1985 and, despite its rarity, is of particular interest as a new iatrogenic entity resulting from CsA administration, mainly in solid organ transplantation. In 1985, two new patients commenced RRT in Europe, and the number increased to 59 in 1991-93. The main reason for undergoing CsA treatment was heart (68%) and liver transplant (22%), and the mean interval from treatment to RRT was 50.2 months, ranging from 5 to 90 months. Patient survival on dialysis was 46% at 4 years, compared to 58% in patients with standard primary nephropathies. Cardiovascular causes (48%) and infection (17%) were the main causes of death. Fabry's disease was introduced as a PRD in the ERA-EDTA Registry in 1985, and since the four to 13 new patients per year have commenced RRT in Europe. It is a sex-linked recessive disorder primarily affecting males (87%), and the mean age at start of RRT was 38 years. Proteinuria, skin lesions and painful paresthesiae were the most common presenting symptoms, and over 70% of the patients were hypertensive and had significant cardiovascular problems at RRT. Patient survival on dialysis was 41% at 5 years, compared to 68% in patients with standard primary nephropathies. Cardiovascular complications (48%) and cachexia (17%) were the main causes of death. Graft survival at 3 years in 33 patients was not inferior to that of patients with standard nephropathies (72% vs 69%), and patient survival after transplantation was comparable to that of patients under 55 years of age with standard PRD. (ABSTRACT TRUNCATED)

Recombinant human erythropoietin.

The characteristics and uses of epoetin alfa (recombinant human erythropoietin) are described, and the issues associated with its use are discussed. The use of epoetin alfa was recently approved by FDA for the treatment of anemia associated with end-stage renal disease. Epoetin alfa acts on burst-forming and colony-stimulating units in the blood to raise hemoglobin and hematocrit levels, thus correcting the patient's anemia. It has a relatively short half-life and may be given either i.v. or s.c. Doses vary and must be adjusted according to the individual patient response. Clinical trials have involved doses ranging from 15 to 500 units/kg three times per week. Treatment causes a dose-related rise in the hematocrit, with subsequent improvement in the quality of life of dialysis patients. Adverse effects include hypertension, iron deficiency, and thrombocytosis. Additional research indicates that epoetin alfa may be effective in the correction of other uncomplicated anemias, such as those related to antineoplastic therapy. Issues facing hospital pharmacists and other health-care professionals include cost (the estimated cost of therapy is $4000 to $8000 per patient per year), appropriate use and potential misuse, use and reimbursement for indications not included in FDA-approved labeling, and restriction to particular prescribers. Because epoetin alfa does not produce therapeutic effects for at least 7 to 14 days, it is an ideal agent for formulary restriction. Epoetin alfa, like other products of biotechnology, will have substantial impact, both therapeutic and economic, on the practice of pharmacy. Hospital pharmacists need to be aware of these new therapies so that they may act quickly and decisively when issues associated with their use arise.

One haplotype matched bone marrow grafts: an investigation using the HLA system as a marker of cellular origin.

HLA antigens were used as markers to study the lymphocyte population in 31 patients with leukaemia, treated with a one-haplotype matched bone marrow transplant (BMT). In 24 patients substained engraftment was achieved and the recipient was repopulated with B and T lymphocytes of donor HLA type. Repopulation occurred at the same rate for lymphocytes of the B and T cell classes, usually within 2 weeks of grafting. In two additional cases bone marrow engraftment was successful but the lymphocyte population was chimeric and cells of both donor and host HLA type were present in the recipient for many weeks. Three patients relapsed after engraftment and peripheral blood lymphocytes were exclusively of host or donor HLA type, or a chimeric population was present. In one chimeric case, peripheral blood T lymphocytes were of donor origin, and B lymphocytes were of host origin. Mononuclear cells in the bone marrow were of host HLA type. The use of the HLA system as a marker is a useful additional approach to determine engraftment or chimerism following an allogeneic one haplotype matched bone marrow transplant.

Topographic sequence of outgrowth of corticospinal axons in the rat: a study using retrograde axonal labeling with Fast blue.

The retrogradely transported dye, Fast blue, was injected into cervical or lumbar segments of the spinal cord of rats during the first days of life in order to label the cell bodies of origin of the corticospinal tract which is growing down the cord during that period. The first corticospinal axons arrive at cervical levels immediately after birth and all arise from a circumscribed group of layer V pyramidal cells in a small region of dorsal parietal cortex. This same cell group provides the corticospinal projection to lumbar segments of the spinal cord, the axons reaching those segments at the end of the first postnatal week. The area of lumbar projecting cells undergoes relatively little expansion and no diminution during subsequent weeks and into adulthood. The area occupied by cortical cells projecting to the spinal cord expands during the first postnatal week, but the axons of all these additional cells do not appear to invade the lower sequents of the spinal cord. By the end of the first week, corticospinal cells can be labeled in a continuous sheet throughout most of the extent of the frontal, parietal and cingulate cortex. During the second and third postnatal weeks, the area sending axons to the upper levels of the spinal cord diminishes and large areas bereft of retrogradely labeled corticospinal cells appear: laterally, in lateral frontal and lateral parietal cortex; dorsally, at the border of frontal and parietal cortex; medially, in medial frontal and cingulate cortex. The more restricted adult pattern is established at the end of the third week. Hence, the first cortical axons to advance down the spinal cord are those that will innervate the lumbar segments in the adult. Later addition of corticospinal axons involves only those projecting to upper cord segments. Within this group there are those which will establish persistent connections from appropriate cortical areas and others that will shortly be eliminated from inappropriate areas.