Only women report increase in pain threshold following fatiguing contractions of the upper extremity.

PURPOSE: The perception of pain in response to a noxious stimulus can be markedly reduced following an acute bout of exercise [exercise-induced hypoalgesia (EIH)]. Sex differences in EIH frequently occur after exercise but may be confounded by the sex differences in muscle fatigue. The purpose was to determine if sex differences in pain relief occur after an exercise protocol when muscle fatigue is similar for both young and older men and women. METHODS: Pain perception of 33 men (15 young) and 31 women (19 young) was measured using a pressure pain stimulus on the left index finger before and after maximal velocity concentric contractions of knee extensors or elbow flexors (separate days). During the 2-min pressure pain test, participants verbally indicated the onset of pain (pain threshold) and reported pain intensity (0-10) every 20 s. RESULTS: Only women experienced an increase in pain threshold (30 ± 27 to 41 ± 32 s) following elbow flexor exercise (trial × sex: p = 0.03). Neither men nor women experienced an increase in pain threshold following knee extensor exercise, and pain ratings were unchanged after exercise with either limb (p > 0.05). The pain response to exercise was similar in young and older adults (trial × age: p > 0.05), despite older adults demonstrating greater fatigability than young adults for the elbow flexor and knee extensor exercise tasks. CONCLUSIONS: Under controlled conditions where muscle fatigue is similar, sex differences in EIH occur in young and older adults that is site specific (upper extremity). Only women experience EIH following acute single limb high-velocity contractions.

Kidney transplantation in children and adolescents: an analysis of United Network for Organ Sharing Database.

Specific pediatric allocation schemes can not only lead to minimization of waiting time, but also to better clinical outcomes for children with end-stage renal disease. The outcome of 4125 deceased donor kidney transplants (DDKT) aged 5-35 years were compared with those of 6456 living donor kidney transplants (LDKT) using univariate and multivariate Cox regression analyses. Unadjusted graft survival rates of DDKT were significantly lower than those of LDKT (hazards ratio [HR] = 1.53; P < .001). Chronic rejection was reported in 416 (10.1%) of 4125 in the DDKT group compared with 537 (8.3%) of 6456 in the LDKT group (P < .001). Among African American recipients, 67 (3.4%) grafts were lost due to noncompliance as a contributory cause of failure compared with 126 (1.5%) among other races (P < .001). A significantly lower incidence of noncompliance was observed in children (0.9%) compared with adolescents (2.2% in ages 10-14; P < .001) and high teens (2.0% in ages 15-20; P < .001). Multivariate analysis showed that adjusted graft survival rates of LDKT were superior to DDKT (HR = 1.22; P < .001) after adjusting for recipient race, recipient age, regraft status, and HLA mismatch. The differences of long-term graft survival rates between DDKT and LDKT have not been reduced (4% at 1 year, 10% at 3 years, and 12% at 5 years for unadjusted survival rates and 3% at 1 year, 6% at 3 years, and 9% at 5 years adjusted survival rates). In our analysis presented here the difference in graft survival between LDKT and DDKT has doubled compared with earlier analysis. Therefore, we recommend LDKT whenever possible as a first choice for pediatric transplant recipients.

Determinants of GFR depression in early membranous nephropathy.

We evaluated the glomerular filtration rate (GFR) in 34 subjects with membranous nephropathy (MN) of new onset. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). A morphometric analysis of glomeruli in the diagnostic biopsy permitted computation of the single-nephron ultrafiltration coefficient (SNK(f)). MN subjects were divided into two groups: moderate or severe, according to whether GFR was depressed by less or more than 50%. SNK(f) was subnormal but similar in moderate and severe MN. In contrast, two-kidney K(f) was significantly more depressed in severe than in moderate MN. We estimated the total number of functioning glomeruli (N(g)) by dividing two-kidney K(f) by SNK(f). Whereas mean N(g) was similar in controls and moderate MN (1.5 and 1.4-1.7 x 10(6), respectively), it was significantly lower in severe MN (0.5 x 10(6)). This degree of glomerulopenia was not reflected in the rate of global sclerosis. We conclude that a combination of depressed SNK(f) (due to foot process broadening) and profound glomerulopenia accounts for GFR depression of >50% early in the course of MN. The cause of the glomerulopenia remains to be elucidated.

Utilizing exercise to affect the symptomology of fibromyalgia: a pilot study.

UNLABELLED: Fibromyalgia (FM), a rheumatological disorder of unknown origin, is characterized by both physical and psychological symptoms. Although inconclusive results have been reported for most treatment modalities, exercise appears to have universal support for decreasing the myriad of symptoms associated with FM. Weaknesses in the literature, however, prevent conclusive statements regarding exercise prescription and concomitant impact on FM symptomology. PURPOSE: The current pilot study attempted to examine the effect of a 24-wk walking program at predetermined intensities on FM. METHODS: Initial design was a randomized control trial with high- and low-intensity exercise groups, and a control group. Subsequent nonrandomized control trials were based on actual exercise behavior. RESULTS: No differences between initial groups were identified. By collapsing groups, heart rate (HR) decreased (P < 0.05) weeks 0-12. Functional impairments were reduced 54% weeks 0-24, with exercise having a large impact (omega2 = 0.30) on this decrease. By reassigning groups, impact of FM on current health status decreased in the low-intensity group (P < 0.05) and increased in the high-intensity group (P < 0.02) weeks 0-24. Omega squared indicated strong influence of exercise on pain (omega2 = 0.51), with greater pain in the high-intensity group. CONCLUSIONS: A larger number of subjects and direct supervision of the training program to increase compliance is necessary to clarify the effects of a walking program on the manifestations of FM. Results indicate that intensity of the walking program is an important consideration. Individuals with FM can adhere to low-intensity walking programs two to three times per week, possibly reducing FM impact on daily activities.

A 100% 2-year graft survival can be attained in high-risk 15-kg or smaller infant recipients of kidney allografts.

BACKGROUND: Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection. HYPOTHESIS: Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status. DESIGN: Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team. RESULTS: Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation. CONCLUSION: One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.

Evolution of incipient nephropathy in type 2 diabetes mellitus.

BACKGROUND: We examined the course of glomerular injury in 12 Pima Indians with long-standing (>8 years) type 2 diabetes mellitus, normal serum creatinine, and microalbuminuria. They were compared with a group of 10 Pima Indians in Arizona with new-onset (<5 years) type 2 diabetes, normal renal function, and normoalbuminuria (<30 mg albumin/g creatinine on random urine specimens). METHODS: A combination of physiological and morphological techniques was used to evaluate glomerular function and structure serially on two occasions separated by a 48-month interval. Clearances of iothalamate and p-aminohippuric acid were used to determine glomerular filtration rate (GFR) and renal plasma flow, respectively. Afferent oncotic pressure was determined by membrane osmometry. The single nephron ultrafiltration coefficient (Kf) was determined by morphometric analysis of glomeruli and mathematical modeling. RESULTS: The urinary albumin-to-creatinine ratio (median + range) increased from 84 (28 to 415) to 260 (31 to 2232) mg/g between the two examinations (P = 0.01), and 6 of 12 patients advanced from incipient (ratio = 30 to 299 mg/g) to overt nephropathy (>/=300 mg/g). A 17% decline in GFR between the two examinations from 186 +/- 41 to 155 +/- 50 mL/min (mean +/- SD; P = 0.06) was accompanied by a 17% decline in renal plasma flow (P = 0.003) and a 6% increase in plasma oncotic pressure (P = 0.02). Computed glomerular hydraulic permeability was depressed by 13% below control values at both examinations, a result of a widened basement membrane and a reduction in frequency of epithelial filtration slits. The filtration surface area declined significantly, however, from 6.96 +/- 2.53 to 5.51 +/- 1.62 x 105 mm2 (P = 0.01), a change that was accompanied by a significant decline in the number of mesangial cells (P = 0.001), endothelial cells (P = 0.038), and podocytes (P = 0.0005). These changes lowered single nephron Kf by 20% from 16.5 +/- 6.0 to 13.2 +/- 3.6 nL/(minutes + mm Hg) between the two examinations (P = 0.02). Multiple linear regression analysis revealed that among the determinants of GFR, only the change in single nephron Kf was related to the corresponding change in GFR. CONCLUSION: We conclude that a reduction in Kf is the major determinant of a decline in GFR from an elevated toward a normal range as nephropathy in type 2 diabetes advances from an incipient to an overt stage.

Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE).

OBJECTIVE: The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. METHODS: The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. RESULTS AND CONCLUSIONS: These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.

Isolation and characterization of Leishmania mutants defective in glycosomal protein import.

Kinetoplastid parasites contain a unique microbody organelle called the glycosome. Several important metabolic pathways found in the cytoplasm of higher eukaryotes are compartmentalized within the glycosome in these pathogens. This fundamental difference between the host and parasite has led to consideration of the glycosome as a potential chemotherapeutic target. The genetic basis of glycosome biogenesis is therefore of great interest. This report describes the isolation of multiple Leishmania mutant cell lines defective in glycosomal protein import, and the detailed characterization of three such lines. The mutants examined partially mislocalize a subset of glycosomal proteins to the cytosol yet retain wild-type numbers of glycosomes. One of the mutants has a mutation in the previously identified LdPEX2 (GIM1) gene. The other two mutants are demonstrated to contain cell-specific lesions in one or more genes distinct from PEX2. The identification of multiple genetically distinct mutants with defects in glycosome import provides an important genetic tool to facilitate the identification of genes involved in glycosome biogenesis.

A new, unique and simple method for ureteral implantation in kidney recipients with small, defunctionalized bladders.

BACKGROUND: Major, almost insurmountable, deterrents exist to the use of the small capacity, defunctionalized, nonneurogenic urinary bladder in renal transplantation, namely, the technical difficulty in performing a satisfactory ureteral implantation with conventional methods and the potential secondary problems with high grade ureteral reflux and obstruction. Alternatives are less than ideal and include transplantation into a bowel-augmented urinary bladder with intermittent self-catheterization, ileal conduit urinary diversion, or avoidance of transplantation and relegating the patient to life-long dialysis. METHODS: Eight consecutive patients (ages 13 months to 29 years) with small, defunctionalized urinary bladders underwent a new method of intravesical implantation of the transplant ureter. The mean capacity of these bladders was 18.5+/-13.1 ml (range 6 to 45 ml), with the bladders defunctionalized for a mean 81.6+/-24.3% of the patients' total lifetime. The technique involved placement of the transplant ureter into a shallow, mucosa-denuded, rectangular trough extending from a superiorly placed ureteral hiatus distally to the trigone. We hypothesized that the mucosal margins on the two lateral aspects of the rectangular trough would grow over the anterior surface of the ureter until they met the advancing mucosal edges from the contralateral side to form a natural neosubmucosal tunnel. RESULTS: Posttransplantation cystoscopic examination demonstrated bladder mucosal regeneration and growth over the ureter, confirming the spontaneous development of a good length neosubmucosal tunnel. All patients demonstrated no evidence of ureteral reflux or ureteral obstruction, whereas an immediate prior cohort of four consecutive patients with bladder capacities < or =30 ml showed that three of four had ureteral reflux (P=0.02) and four of four developed hydronephrosis (P=0.002). All urinary bladders in the present cohort enlarged to expected normal or nearnormal capacities. Serum creatinines were stable throughout the entire follow-up period, with the exception of one patient who had rejection episodes. Two patients had urinary tract infections posttransplantation, but there were no episodes of acute pyelonephritis. CONCLUSIONS: This novel technique for ureteral implantation successfully capitalizes on the regenerative potential of the bladder mucosa, resulting in a physiological, anatomically natural, and very effective neosubmucosal tunnel. It appears to guarantee success against both ureteral reflux and obstruction, no matter how small the urinary bladder, and offers no hindrance to enlarging the bladder to near normal capacity posttransplantation. The implantation technique is simple and safe, and its use should eliminate the reluctance to use these bladders. Moreover, this procedure offers a major incentive for the successful rehabilitation of small, defunctionalized, nonneurogenic bladders after kidney transplantation.

The role of the podocyte in glomerulosclerosis.

Focal segmental glomerulosclerosis is a pathological hallmark of many forms of progressive renal disease. The 'classic' lesion, based on the adhesion of the capillary tuft to Bowman's capsule, results from the loss of podocytes from the capillary basement membrane. The recently described 'collapsing' variant, in contrast, has an apparent excess of extracapillary cells, which may represent dedifferentiated, 'dysregulated' podocytes.

A dominant negative mutation in the GIM1 gene of Leishmania donovani is responsible for defects in glycosomal protein localization.

Kinetoplastid protozoa contain a unique microbody organelle called the glycosome. Several important metabolic pathways are compartmentalized within the glycosome that are found in the cytoplasm of higher eukaryotes. We have previously reported the identification of a Leishmania donovani cell line called gim1-1, in which several normally glycosomal proteins are partially mislocalized to the cytoplasm. The GIM1 gene complements the defect and restores import of proteins to the glycosome. Here we demonstrate that GIM1 encodes an integral membrane protein of the glycosome. We also report that the mutant gim1-1 allele behaves as a dominant negative mutation. Introducing the gim1-1 allele extrachromasomally led to mislocalization of a glycosomal reporter protein even in wild-type cells. Gene disruption experiments in heterozygous GIM1/gim1-1 cells showed that when the mutant gim1-1 allele was lost, cells re-established normal glycosomal protein localization. Interestingly, no disruptions of the wild-type allele were obtained. These data indicate that a dominant negative mutation in the GIM1 gene is the sole genetic lesion responsible for the glycosomal defects in gim1-1, and suggest that GIM1 is an essential gene in Leishmania.

Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow.

BACKGROUND: Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved. METHODS: Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume. RESULTS: Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl. CONCLUSIONS: This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Progression of glomerular diseases: is the podocyte the culprit?

The stereotyped development of the glomerular lesions in many animal models and human forms of progressive renal disease suggests that there are common mechanisms of disease progression. We propose the outline of such a mechanism based on following aspects: (1) The glomerulus is a complex structure, the stability of which depends on the cooperative function of the basement membrane, mesangial cells and podocytes, counteracting the distending forces originating from the high glomerular hydrostatic pressures. Failure of this system leads to quite uniform architectural lesions. (2) There is strong evidence that the podocyte is incapable of regenerative replication post-natally; when podocytes are lost for any reason they cannot be replaced by new cells. Loss of podocytes may therefore lead to areas of "bare" GBM. which represent potential starting points for irreversible glomerular injury. (3) Attachment of parietal epithelial cells to bare GBM invariably occurs when bare GBM coexists with architectural lesions, leading to the formation of a tuft adhesion to Bowman's capsule, the first "committed" lesion progressing to segmental sclerosis. (4) Within an adhesion the tuft merges with the interstitium, allowing filtration from perfused capillaries inside the adhesion towards the interstitium. The relevance of such filtration is as yet unclear but may play a considerable role in progression to global sclerosis and interstitial fibrosis.

Mechanisms of progressive glomerular injury in membranous nephropathy.

Glomerular function and structure were serially evaluated in 15 patients with membranous nephropathy who exhibited relapsing nephrosis and chronic depression of GFR. GFR declined from 56+/-8 (mean+/-SEM) at onset to 31+/-4 ml/min per 1.73 m2 after a 2- to 5-yr period of observation (P < 0.05). An analysis of filtration dynamics suggested persistent elevation of net ultrafiltration pressure. To examine a possible role for declining intrinsic glomerular filtration capacity as the basis for the observed hypofiltration, glomeruli in the baseline and a repeat biopsy (performed after a median of 28 mo) were subjected to morphometric analysis and mathematical modeling. Analysis of the baseline biopsy revealed a reduction in filtration slit frequency and thickening of the glomerular basement membrane, lowering computed hydraulic permeability by 66% compared with normal kidney donors. In contrast, filtration surface area was increased by 37% as a result of glomerular hypertrophy. The repeat biopsy revealed persistent depression of hydraulic permeability, primarily owing to foot process broadening. An additional finding was a decrease in filtration surface area from baseline in patent glomeruli, possibly due to encroachment on the capillary lumen of an increasingly widened basement membrane. Also, a striking increase in the prevalence of global glomerulosclerosis from 7+/-2% to 23+/-4% was found between the two biopsies, suggesting a significant loss of functioning nephrons. It is concluded that hypofiltration in membranous nephropathy is the consequence of a biphasic loss of glomerular ultrafiltration capacity, initially owing to impaired hydraulic permeability that is later exacerbated by a superimposed loss of functioning glomeruli and of filtration surface area.

Superior outcomes in pediatric renal transplantation.

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

A frequent pathway to glomerulosclerosis: deterioration of tuft architecture-podocyte damage-segmental sclerosis.

Lesions in glomerular architecture include mesangial expansion, capillary ballooning, capillary unfolding and microaneurysm formation. Such lesions appear to develop in response to mechanical overextension. A frequent pathway to segmental glomerulosclerosis starts from capillary ballooning and unfolding. Podocytes supporting those deranged capillaries are exposed to increased mechanical stress. This may lead to podocyte injury terminating in detachments from the GBM. Naked GBM areas at peripheral capillary loops allow the attachment of parietal cells to the GBM, i.e. the formation of a tuft adhesion to Bowman's capsule. An adhesion has a strong tendency to progress to segmental sclerosis.

Structure-stabilizing forces in the glomerular tuft.

The glomerular tuft is constantly exposed to considerable expansile forces resulting from high capillary pressures. Counterforces must be generated in order to maintain structural stability. This review analyzes those structures of the glomerular tuft capable of developing such stabilizing forces. Two systems are described. A basic system consists of the glomerular basement membrane (GBM) and the mesangium. The GBM represents the main skeletal element of the glomerular tuft. In general, opposing portions of the GBM are bridged by contractile mesangial cell processes, generating inwardly directed forces that balance the expansile forces resulting from pressure gradients across the GBM. A second structure-stabilizing role of the podocytes appears to be superimposed on this system. Podocytes are attached to the GBM by numerous foot processes that contain a contractile system. The foot process attachments probably stabilize small patches of the underlying GBM, counteracting local elastic distension. In addition, podocytes may contribute to the stabilization of the folding pattern of the tuft by linking neighboring capillary loops to each other.

Glomerular hypertrophy after subtotal nephrectomy: relationship to early glomerular injury.

Structural adaptations in response to approx. 70% nephrectomy were studied in male Sprague-Dawley rats. Rats developed systemic hypertension as well as progressive albuminuria after nephrectomy. At 18-26 weeks after nephrectomy (n = 6) or sham treatment (n = 6) kidneys were perfusion-fixed and examined by light and electron microscopy. Glomerular tuft volume (+140%), capillary volume (+151%) and length (+77%), mesangial volume (+115%), podocyte volume (+96%), glomerular basement membrane surface area (+107%) and filtration slit length (+85%) were all significantly greater in nephrectomized rats. The incidence of segmental glomerular sclerosis was low and variable among these rats, but was significantly higher than in controls (P = 0.037). Urinary albumin excretion was elevated in the nephrectomized rats (89 +/- 72 SD mg/day vs 11 +/- 11 mg/day in control rats, P = 0.01) and correlated significantly with the incidence of sclerosis (r = +0.8311, P < 0.05). The relationships of the level of albuminuria and the sclerosis rate to various morphometric parameters were examined by regression analysis for the nephrectomy group. A significant negative correlation was found between albuminuria and average tuft volume (r = -0.8136) and glomerular basement membrane surface area (r = -0.8168). Both sclerosis rate and albuminuria showed negative correlations with filtration slit length (r = -0.8180 and r = -0.8598). These findings suggest that under some circumstances, glomerular hypertrophy may prevent or ameliorate the early stages of glomerular injury after subtotal nephrectomy.

Baseline data on the delivery of clinical preventive services provided by nurse practitioners.

The National Alliance of Nurse Practitioners (NANP) was one of five primary care provider groups that participated in a national government-sponsored survey on clinical preventive services (CPSs). The survey was based on 17 of the Healthy People 2000 national health objectives related to CPSs. This survey was sent to 2000 randomly selected nurse practitioners (NPs) to obtain information concerning the percentage of their patients who "routinely" receive the specified assessment and intervention services. Data from 892 completed and returned survey instruments indicated that NPs already exceed the Healthy People 2000 objective targets in some important clinical preventive assessment and intervention areas. They are close to the targets in a number of other CPS areas. In some areas, however, NP provision of preventive services was reported to be below the Healthy People 2000 targets. This data has far-reaching implications for NP practice, basic and continuing education, and curriculum reform.