Enhancing soil organic carbon, particulate organic carbon and microbial biomass in semi-arid rangeland using pasture enclosures.

BACKGROUND: Rehabilitation of degraded rangelands through the establishment of enclosures (fencing grazing lands) is believed to improve soil quality and livelihoods, and enhance the sustainability of rangelands. Grazing dominated enclosure (GDE) and contractual grazing enclosure (CGE) are the common enclosure management systems in West Pokot County, Kenya. Under CGE, a farmer owning few animals leases the enclosure to households with relatively more livestock, while GDE is where the livestock utilizing the enclosure are purely owned by the farmer. Livestock management in both systems is via the free-range system. This study evaluated the effect of enclosure management on total soil organic carbon (SOC), particulate organic carbon (POC) and microbial biomass carbon (MBC) and nitrogen (MBN) as key indicators of soil degradation at 0-40 cm depth. The two enclosure systems were selected based on three age classes (3-10, 11-20 and > 20 years since establishment) (n = 3). The adjacent open grazing area (OGR) was used as a reference (n = 9). RESULTS: Relative to OGR, the pasture enclosures significantly decreased soil bulk density and increased the concentrations of total organic C, POC, MBC and MBN compared to the degraded OGR (P < 0.001). Significantly higher concentrations of POC and MBC was recorded in GDE than CGE (P = 0.01). The POC accounted for 24.5-29.5% of the total SOC. MBC concentrations ranged from 32.05 ± 7.25 to 96.63 ± 5.31 µg C g-1 of soil in all grazing systems, and was positively correlated with total SOC and POC (P < 0.001). The proportional increase in POC and MBC was higher in GDE (56.6 and 30.5% respectively) compared to CGE (39.2 and 13.9% for POC and MBC respectively). CONCLUSIONS: This study demonstrated that controlling livestock grazing through the establishment of pasture enclosures is the key strategy to enhance total SOC, POC, MBC, and MBN in degraded rangelands; a precondition for improving soil quality. Therefore, the establishment of enclosures is an effective restoration approach to restore degraded soils in semi-arid rangelands.

Immune response to bacterial dextrans. II. T cell control of antibody isotypes.

The isotype distribution of Dextran B 512 (Dex)-specific plaque-forming cells (PFC) and serum antibodies was studied after in vivo immunization in C57BL/6 mice. Although IgG2b and IgG3 could also be detected in most individuals, the majority of non-IgM PFC were of the IgA isotype. All classes other than IgM were T cell-dependent, as shown by their complete absence in athymic "nude" mice. This unusual isotype pattern was further investigated by studying the antibody responses to the same Dex epitope coupled to a protein carrier, and to a different hapten coupled to the carrier Dex or to a protein. The results show that IgA responses are epitope-related and selectively associated with anti-Dex antibodies: no IgA PFC are detected against a hapten coupled to Dex or proteins, while the enhanced levels of helper cell reactivity provided by protein carrier to Dex result in the appearance of IgG1 antibodies in addition to IgA. These results indicate that T cells that modulate isotype patterns in these responses can discriminate between Dex- and DNP-specific B cells in the response to the same carrier. Since the same idiotype is detected on a large fraction of the IgM and IgA anti-Dex response and antiidiotypic helper cells have previously been detected in normal C57BL/6 mice, we suggest that idiotype-specific T cells control the production of IgA antibodies upon immunization with Dex.

A 4-year, cluster-randomized, controlled childhood obesity prevention study: STOPP.

OBJECTIVE: To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children. DESIGN: Cluster-randomized, controlled study. SUBJECTS: A total of 3135 boys and girls in grades 1-4 were included in the study. METHODS: Ten schools were selected in Stockholm county area and randomized to intervention (n=5) and control (n=5) schools. Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools. Physical activity (PA) was aimed to increase by 30 min day(-1) during school time and sedentary behaviour restricted during after school care time. PA was measured by accelerometry. Eating habits at home were assessed by parental report. Eating disorders were evaluated by self-report. RESULTS: The prevalence of overweight and obesity decreased by 3.2% (from 20.3 to 17.1) in intervention schools compared with an increase of 2.8% (from 16.1 to 18.9) in control schools (P<0.05). The results showed no difference between intervention and controls, after cluster adjustment, in the longitudinal analysis of BMIsds changes. However, a larger proportion of the children who were initially overweight reached normal weight in the intervention group (14%) compared with the control group (7.5%), P=0.017. PA did not differ between intervention and control schools after cluster adjustment. Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention. There was no difference between children in intervention and control schools in self-reported eating disorders. CONCLUSIONS: A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home. The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA.

Physical activity in children measured by accelerometry: stability over time.

The aim of this study was to examine the stability of objectively measured physical activity in Swedish children and to study variables that predicted physical activity and body mass index standard deviation score (BMI SDS) at follow-up. A total of 97 children provided valid repeated measurements of physical activity between 2002 and 2005. The children were on average 7.5 years at baseline (SD+/-0.92) and 9 years at follow-up (SD+/-0.92). The mean follow-up time was approximately 1.5 years (mean 558 days, SD+/-224). An accelerometer (Actiwatch, Cambridge Neurotechnology Ltd., Cambridge, UK) was used to measure physical activity during 7 consecutive days. Yearly weight and height were examined and BMI SDS was calculated. Baseline physical activity was significantly correlated with physical activity at follow-up (r=0.59) with a stronger correlation for boys (r=0.72) than for girls (r=0.51). High physical activity levels were more stable (r=0.74) than low physical activity levels (r=0.55). Physical activity at follow-up was explained by physical activity at baseline and season (R(2)=0.46) whereas BMI SDS at follow-up was explained by BMI SDS at baseline and age (R(2)=0.90). The results of this study suggest that physical activity levels are fairly stable in 6-10-year-old children.

Can DXA predict fractures in renal transplant patients?

Renal transplant patients have a high prevalence of osteopenia, osteoporosis and fractures. The aim of the study was to investigate whether dual-energy x-ray absorptiometry (DXA) is of value to predict fractures. In 1995-2007, 238 renal transplant patients underwent 670 DXA investigations. Osteopenia (46.0%), osteoporosis (13.9%) and absolute bone mineral density (BMD) (median 0.9, range 0.4-2.0 g/cm(2)) in the hip region were used to evaluate fracture risk. Data on fractures were collected at the occasion of each DXA, and a questionnaire was filled in by 191 patients at regular outpatient visits. Reported fractures were verified by consultation of medical records. In all, 46 patients had 53 fractures. Cumulative hazard of fracture was significantly different among normal BMD, osteopenia and osteoporosis in the hip (p < 0.0001). A Cox proportional hazard analysis also including age, gender and diabetic nephropathy showed significantly increased fracture risk for osteoporosis (3.5 times, CI 1.8-6.4, p = 0.0001) as well as for osteopenia (2.7 times, 1.6-4.6, p = 0.0003). A significantly increased risk was also found with absolute BMD estimates below the median. Osteopenia and an absolute bone density below 0.9 g/cm(2) in the hip region confer an increased risk of fracture.

Intermediate tree cover can maximize groundwater recharge in the seasonally dry tropics.

Water scarcity contributes to the poverty of around one-third of the world's people. Despite many benefits, tree planting in dry regions is often discouraged by concerns that trees reduce water availability. Yet relevant studies from the tropics are scarce, and the impacts of intermediate tree cover remain unexplored. We developed and tested an optimum tree cover theory in which groundwater recharge is maximized at an intermediate tree density. Below this optimal tree density the benefits from any additional trees on water percolation exceed their extra water use, leading to increased groundwater recharge, while above the optimum the opposite occurs. Our results, based on groundwater budgets calibrated with measurements of drainage and transpiration in a cultivated woodland in West Africa, demonstrate that groundwater recharge was maximised at intermediate tree densities. In contrast to the prevailing view, we therefore find that moderate tree cover can increase groundwater recharge, and that tree planting and various tree management options can improve groundwater resources. We evaluate the necessary conditions for these results to hold and suggest that they are likely to be common in the seasonally dry tropics, offering potential for widespread tree establishment and increased benefits for hundreds of millions of people.

Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli.

Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.

Diabetic glomerulopathy. Structural characteristics of the early and advanced stages.

Studies of the glomerular structure in diabetes mellitus have helped to elucidate the basis for some functional abnormalities. The decline in glomerular filtration occurring in many long-term diabetics is a functional disorder of great clinical importance. Quantitative structural studies of the glomeruli in diabetics at different stages of disease are necessary to learn about the development of structural changes leading to the end-stage kidney disease. Preliminary results of a study of glomeruli from long-term diabetics with clinical nephropathy are compared with those obtained in control subjects and in diabetics within the first 5 yr of disease. In the long-term diabetics the peripheral basement membrane thickness was doubled. On the average, mesangial regions occupied nearly 60% of the total tuft volume as compared with 33% in the early stages. A marked accumulation of basement membrane material in the mesengial regions had taken place so that 85% of the total basement membrane material of the tufts (i.e., peripheral basement membrane in the capillary walls plus mesangial basement membrane-like material) was localized within the mesangial regions. In the early stages equal amounts were found at these two different sites. The distribution of the lesions within the kidney is under investigation in a light microscopic study of autopsy material from long-term diabetics with varying degrees of glomerulopathy. The severity of the diabetic glomerulopathy was quantitated separately within the superficial and the deep cortical zones. The results showed that there was no tendency toward increased severity in the deep glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the impact of glycemic control, blood pressure, lipid levels, glomerular filtration rate (GFR), age, and duration of IDDM on the degree of structural glomerular changes in the transitional stage of microalbuminuria. RESEARCH DESIGN AND METHODS: Fifteen adolescents (seven boys and eight girls) with > 5 years of duration of IDDM and with low-grade microalbuminuria (15-30 micrograms/min) participated. Seventeen living kidney donors served as healthy control subjects. Five-year mean HbA1c; 5-year mean systolic and diastolic blood pressure; GFR, cholesterol, and triglycerides 2-5 years before renal biopsy; age; and duration of IDDM were investigated and related to basement membrane thickness (BMT), mesangial and matrix volume fractions, and the overall glomerulopathy index [(BMT/10 + mat/glom, %) + matrix star volume]. RESULTS: BMT and the overall diabetic glomerulopathy were increased in diabetic patients as compared with control subjects (P < 0.001), whereas matrix volume fraction, but not mesangial volume fraction, tended to be increased (P = 0.11). In multivariate analysis, BMT was predicted by 5-year mean HbA1c, diabetes duration, and previous GFR (R2 = 0.71, P = 0.003). With matrix volume fraction as the dependent variable, BMT and diabetes duration were the only significant determinants (R2 = 0.63, P = 0.003). Diabetes duration, 5-year mean HbA1c, and GFR were the variables with an independent influence on the overall diabetic glomerulopathy index (R2 = 0.72, P = 0.003). Preceding blood pressure and lipid levels or age had no significant independent influence on these morphometric measures. CONCLUSIONS: In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.

Time as a risk factor in diabetic nephropathy.

Eighteen individuals with IDDM (type I) and diabetic nephropathy in whom the initial glomerular filtration rate (GFR) was reduced but not below 60 ml/min per 1.73 m2 were observed for an average of 3 yr. The rate of further decline of GFR was found to range between -2 and 21 ml/min/yr. The duration of diabetes until the GFR was first found to be reduced varied between 14 and 33 yr and was not correlated to the ensuing rate of decline in GFR (r = -0.13). In 10 individuals who developed uremia 40 yr or more after onset of IDDM, the development of persistent proteinuria was followed by hypertension and increased serum creatinine 2 yr later and by terminal uremia after an average of 8 yr. This is also the normal time span for individuals who develop terminal uremia after shorter duration of diabetes. We conclude that the course of clinical diabetic nephropathy is not more favorable in individuals with late onset of this complication and that there is no point at which a person with diabetes can be considered to be spared from developing diabetic nephropathy.

Effect of captopril on renal hemodynamics in the treatment of resistant renal hypertension.

The effects of 6 weeks of treatment with captopril on the renal hemodynamics of 16 patients with treatment-resistant renal hypertension (six had diabetic nephropathy, seven had other renal parenchymatous disease, and three had renovascular disease) were studied. Significant changes in glomerular filtration rate, filtration fraction, plasma renin activity, urinary aldosterone, and mean blood pressure were noted in the patients with renal parenchymatous disease, but not in those with diabetic nephropathy. Renal blood flow remained unchanged in all patients. Captopril was well tolerated.

Guanfacine in essential hypertension: effects during rest and isometric exercise.

The antihypertensive effects of guanfacine (0.5 to 4 mg daily) were investigated for 1 yr in 13 patients with essential hypertension. Blood pressure (BP) and heart rate (HR) response was measured during isometric exercise (handgrip) before starting the therapy, after 1 yr of treatment, and 2 wk after withdrawal. Guanfacine in once-daily dosage reduced BP during rest (supine BP: control, 175 +/- 6/103 +/- 4 mm Hg; 1 yr guanfacine, 161 +/- 5/91 +/- 3 mm Hg). Steady-state plasma concentrations after 1 yr were 4.1 +/- 0.59 ng/ml. Resting plasma norepinephrine (NE) and epinephrine (E) levels were lower during active therapy than 2 wk after withdrawal (guanfacine and control: plasma NE, 0.27 +/- 0.03/0.64 +/- 0.13 ng/ml; plasma E, 0.09 +/- 0.02/0.17 +/- 0.05 ng/ml). The relative reduction of plasma catecholamines (guanfacine and withdrawal) was of the same order during handgrip exercise as during supine rest. During isometric handgrip exercise, BP was lower during guanfacine therapy than before treatment and 2 wk after withdrawal, but the increment in BP during handgrip exercise was not affected by the drug despite the lower BP values on therapy. Our data indicate that the central alpha 2-agonist action of guanfacine reduces sympathoadrenal function equally during rest and isometric exercise.

Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans.

OBJECTIVE: To measure cardiac and other effects of thioridazine and relate these to the plasma concentration of the parent drug and its principal metabolites. METHODS: A double-blind, randomized-order crossover study involving nine healthy male subjects compared the effects of single doses of thioridazine (10 mg and 50 mg) with placebo. Plasma concentrations of thioridazine and its ring sulfoxide, side-chain sulfoxide, and side-chain sulfone metabolites were measured, together with effects on the ECG, blood pressure, salivary flow, and a batch of psychomotor tests for 72 hours after administration. RESULTS: Thioridazine, 50 mg, reduced standing systolic blood pressure (mean peak changes from baseline [95% CI] -32 mm Hg [-55, 10 mm Hg]; p < 0.01 versus placebo) and diastolic blood pressure (-14 mm Hg [-26, -2 mm Hg]; p < 0.05), increased standing heart rate (7 beats/min [-1, 16 beats/min]; p < 0.05), impaired psychomotor function, and prolonged the JT (20 ms1/2 [7, 34 ms1/2]; p < 0.05), QTa (22 ms1/2 [8, 36 ms1/2]; p < 0.05), and QTc (22 ms1/2 [11, 33 ms1/2]; p < 0.01) intervals, but had no effect on QT dispersion (-12 ms1/2 [-31, 6 ms1/2]). Thioridazine, 1.0 mg, also significantly increased QTc, but the effect was less marked (9 ms1/2 [-1, 19 ms1/2]; p < 0.05). Plasma thioridazine and metabolite concentrations did not correlate significantly with these effects. Maximum effects on QTc occurred after peak concentrations of thioridazine but before peak concentrations of the ring sulfoxide and side-chain sulfone metabolites. CONCLUSIONS: These data suggest that thioridazine has dose-related effects on ventricular repolarization and that the parent drug causes an important proportion of these effects, although its metabolites may also contribute.

Representation of the forepaw in the feline cuneate nucleus: a transganglionic transport study.

The projection of forelimb nerves innervating the paw to the cuneate nucleus was studied in the cat by the transganglionic transport method. Exposure of a single digital nerve to the tracer (a conjugate of horseradish peroxidase to wheat-germ agglutinin) resulted in a longitudinal sequence of labeled patches throughout the extent of the nucleus. In the middle region the labeled patches coincided with the location of the cell clusters that are characteristic of this part of the nucleus. A very precise somatotopic termination pattern was found in the middle region of the nucleus. Afferent fibers from the palm were represented superficially close to the dorsal rim. The digits were represented in a mediolateral sequence, with the first digit in the dorsolateral part of the nucleus and the fifth digit in the dorsomedial part. The ventral surfaces of the digits were represented superficial to the dorsal surfaces. The dorsum of the paw was represented close to the center of the nucleus. A similar somatotopic organization, but much less detailed, was found in the rostral and caudal regions of the cuneate nucleus. These dissimilarities in somatotopic detail between the different cytoarchitectonic regions of the cuneate nucleus probably reflect differences in function between these regions.

The central projection of muscle afferent fibres to the lower medulla and upper spinal cord: an anatomical study in the cat with the transganglionic transport method.

The projection of muscle afferent fibres to the medulla oblongata and upper spinal cord was studied in the cat by using transganglionic transport of wheat germ agglutinin-horseradish peroxidase conjugate. The results demonstrate a precise, musculotopic termination pattern in the external cuneate nucleus; thus, fibres from the intrinsic muscles of the paw terminate medially; those from forearm, arm, and shoulder muscles terminate progressively more laterally; and those from neck and thoracic muscles terminate in the ventrolateral and dorsolateral parts, respectively. Muscle afferent fibres to the main cuneate nucleus terminate in the ventral "reticular" region of the nucleus, with a sparse projection also to the ventral part of the rostral and caudal regions, including the base of the dorsal horn. Fibres from the neck muscles terminate slightly more laterally in the ventral region than do those from the limb muscles, but otherwise, and thus contrary to the case in the external cuneate nucleus, no topographic organization was detected. In the spinal cord, projection was found to laminae I and V, and from the musculature of the back of the neck to the central cervical nucleus.

The somatotopic organization of forelimb cutaneous nerves in the brachial dorsal horn: an anatomical study in the cat.

The projection of forelimb cutaneous nerves to the brachial dorsal horn was studied in the cat by the transganglionic transport method. The results demonstrate a precise somatotopic termination pattern. Afferent nerves from the paw occupy the largest area, with the palm represented most medially in the dorsal horn, followed progressively more laterally by the representations for the palmar and dorsal surfaces of the digits and the dorsum of the paw. The digits are represented in a longitudinal sequence, with the first digit in the caudal part of C6 and the fifth in the caudal part of C8. The projections of the wrist and arm are split, with the line of discontinuity located along the ventral surface of the limb, so that the radial side is represented rostral to the paw and the ulnar side caudal to the paw, with the dorsal surface of the arm represented lateral to the paw. Nerves innervating the skin of the back project to the lateralmost part of the dorsal horn. The degree of overlap or separation of the terminal fields of the nerves along the mediolateral axis of the dorsal horn seems to correspond to the degree of overlap or separation of the peripheral innervation fields. However, along the rostrocaudal axis there appears to be an overlap for which there is no counterpart peripherally.

A controlled study of the effects of isosorbide mononitrate on arterial blood pressure and pulse wave form in systolic hypertension.

OBJECTIVE: To determine the effect of an extended-release nitrate preparation on the arterial pulse wave and blood pressure of patients in whom systolic blood pressure was elevated in part by exaggerated pulse-wave reflectance. DESIGN: A double-blind randomized placebo-controlled crossover study was carried out. PATIENTS AND METHODS: The subjects were ten elderly patients with systolic hypertension resistant to conventional anti-hypertensive therapy. Pharmacodynamic responses to 2-week courses of placebo/isosorbide mononitrate (ISMN) were assessed in seven subjects by an ambulatory blood pressure monitor, and in all ten subjects by standard sphygmomanometry, arterial pulse-wave analysis and measurement of plasma nitrate concentration during peak and trough. RESULTS: Ambulatory systolic blood pressure was decreased by ISMN (P < 0.02) between 1000 and 2200 h. Ambulatory diastolic blood pressure fell with ISMN (P < 0.01) during the last 4 h of this period. At peak plasma nitrate levels, ISMN decreased the aortic systolic blood pressure (P < 0.01), ejection peak (P < 0.02) and augmentation component (P < 0.001) of the pulse wave; heart rate increased slightly (P < 0.03). CONCLUSION: ISMN has a role as an adjunct in the anti-hypertensive therapy of patients with refractory systolic hypertension due to exaggerated pulse-wave reflectance.

Low absolute glomerular filtration rate in the living kidney donor: a risk factor for graft loss.

BACKGROUND: There is no defined lower acceptable level of glomerular filtration rate (GFR) in potential living kidney donors. Considerations focus on the risk for the donor. We wanted to evaluate the outcome in the recipient in relation to the GFR of the living donor. METHODS: There were 344 living donated kidney transplantations performed January 1985 through February 1997 which were evaluated. Two thirds of the donors shared one haplotype with the recipient and 15% shared both. Of the donors 18% were above age 60. The median follow-up time (until graft loss) was 63 months. Before nephrectomy, the donors' GFR had been measured by isotope clearance. RESULTS: Twenty-six donors (7.6%) had an absolute GFR below 80 ml/min, i.e. not adjusted to 1.73 m2 body surface area (BSA). Cumulative graft survival, censored for graft loss because of death of the patient, was significantly reduced in recipients of grafts from donors with GFR <80 ml/min. A significant correlation between GFR and donor age was observed, but donor age per se was not identified as a risk factor for graft loss. In a Cox stepwise proportional hazards analysis, the relative risk for graft loss was 2.28 with a GFR below 80 ml/min (confidence interval 1.183-4.383, P=0.014) and with sharing one or both haplotypes 0.56 (0.313-0.988, P=0.046) and 0.36 (0.139-0.912, P=0.03), respectively. CONCLUSIONS: An absolute GFR below 80 ml/min in the living donor more than doubles the risk of graft loss. This fact should be considered when definitions of acceptable limits for donor GFR are discussed.

Systemic vasculitis in a kidney transplant population.

BACKGROUND: Systemic vasculitis as original disease might adversely influence the result of kidney transplantation. METHODS: The clinical course after 32 transplantations to 26 patients with microscopic polyangiitis, Wegener's granulomatosis, Henoch-Schonlein purpura, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, or Goodpasture's disease was evaluated. The median follow-up time was 82 months (range, 4-132 months). Frozen sera from 25 transplantations were analyzed for Goodpasture antibodies, myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA), and proteinase 3 ANCA. RESULTS: Survival of patients and grafts did not differ between patients and matched controls. Recurrent vasculitis occurred with seven grafts (four patients with microscopic polyangiitis or Wegener's granulomatosis, two patients with Henoch-Schonlein purpura, and one patient thrombotic thrombocytopenic purpura). New-onset hematuria was the initial renal symptom in five patients. Treatment with corticosteroids, cyclophosphamide, and/or plasma exchange was most often effective, but two grafts were lost. Proteinase 3 ANCA titers were increased to 12-738 U/ml before seven transplants. The patient with the lowest titer lost his graft due to recurrence, two other patients had reversible recurrence after 1 year and 5 years, two patients lost their grafts due to unknown/unrelated causes, and two patients' grafts remain without recurrence. Myeloperoxidase ANCA were increased to 22-39 U/ml before two transplants, which have been uneventful for 4 years. CONCLUSIONS: An awareness of the small but perpetual risk of recurrence facilitates early treatment that may save the transplant. Testing for hematuria and early transplant biopsies, and possibly monitoring of ANCA titers, are essential, but pretransplant ANCA titers have no predictive value in asymptomatic patients. Results of kidney transplantation in patients with vasculitis are as good as in other patients.

Breast-feeding during treatment with cyclosporine.

BACKGROUND: Mothers treated with cyclosporine (CsA) have previously not been allowed to breast-feed due to the reported accumulation of the drug in breast milk. The purpose of this study was to evaluate the consequences of allowing breast-feeding. METHODS: Seven infants were breast-fed by mothers who had undergone kidney transplantation alone (n=5) or simultaneous kidney and pancreas transplants (n=2). In addition to CsA, all mothers received prednisolone at 5-7.5 mg/day and six mothers received azathioprine at 50-100 mg. CsA concentration was measured in the whole blood of mothers and babies and in breast milk. Serum creatinine was measured in babies 1 week after birth and after 4-12 months of breast-feeding. RESULTS: Blood CsA levels ranged from 55 to 130 ng/ml in mothers (12-hr trough), 50 to 227 ng/ml in breast milk (mean for each woman), and was below the detection limit of 30 ng/ml in all infants. Breast milk concentration ranged from 87 to 440 ng/ml in 16 samples obtained at various time points from one mother. Infants' serum creatinine ranged from 25 to 54 micromol/L at 1 week after birth and 23-52 micromol/L after breast-feeding. All babies thrived. CONCLUSIONS: Breast-fed infants of mothers treated with CsA received less than 300 microg per day of CsA and absorbed undetectable amounts. There were no demonstrable nephrotoxic effects or other side effects. Thus, women with kidney transplants could be allowed to breast-feed.