Severe thrombocytopenia and clinical bleeding associated with rituximab infusion in a lymphoma patient with massive splenomegaly without leukemic invasion.
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Biomedical subjects
E Bartoli
Publications and source records attributed to E Bartoli.
[Epidemiology and natural history of cholelithiasis].
Gallstone disease is relatively common, affecting approximately 15% of the population in Europe and North America, but it is benign since its natural history remains asymptomatic in nearly 80% of cases. The stones are predominantly cholesterol derived in 80% and pigmentary in 20% of cases. Recent epidemiologic studies using ultrasound examination have determined the factors favouring lithogenesis, in addition to those that are already wellknown, such as age, obesity, female gender, high blood triglyceride levels and multiparity, the risk is correlated with high, frequent variations in weight, with intake of certain drugs and with alimentary habits. In addition, physical exercise plays a protective role against the development of symptomatic gallstone disease.
Adult↗
Systemic and intratubular effects of cyclosporin-A and tacrolimus on the rat kidney.
Cyclosporin-A and tacrolimus can cause hypertension and renal failure through endothelin receptors. The importance of tubular function was never investigated. The aim of this study was to compare the effects of intratubular injection of cyclosporin-A and tacrolimus with effects observed during systemic infusion. In 20 rats, either cyclosporin-A or tacrolimus was infused, 30 and 1 mg/kg i.v., respectively, in 30 min. Before and after administration, glomerular filtration rate, single nephron filtration rate, proximal and distal absolute reabsorption and percent reabsorption were measured by clearance and micropuncture techniques. In 22 other rats, single nephron filtration rate, absolute reabsorption, percent reabsorption, were measured at the last proximal and early distal tubules before and during intraluminal microinjection of either cyclosporin-A or tacrolimus. During cyclosporin-A and tacrolimus i.v. infusion, glomerular filtration rate fell from 536+/-43 to 448+/-37 microl/min (P<0.026) and from 408+/-33 to 284+/-81 microl/min (P<0. 02), single nephron filtration rate from 26.4+/-2.0 to 20.6+/-1.9 (P<0.002) and from 21.6+/-2.2 to 17.4+/-2.0 nl/min, respectively (P<0.02). The last proximal absolute reabsorption remained unchanged with cyclosporin-A (16.8+/-2.2 vs. 15.1+/-1.7 nl/min, P>0.444), but was slightly reduced by tacrolimus (14.4+/-1.7 vs. 11.3+/-1.7 nl/min, P<0.05). During microinjection, single nephron filtration rate was increased by cyclosporin-A (20+/-1 vs. 63+/-8 nl/min, P<0.0001), and tacrolimus (from 17+/-2 to 49+/-9 nl/min, P<0.0001), and so was reabsorption, independent of the sampling site. Cyclosporin-A and tacrolimus, indeed, raise single nephron filtration rate directly when injected intraluminally. Since this effect occurs in the direction opposite to that recorded during systemic infusion, it must be mediated through different pathways. The i.v. infusion of cyclosporin-A, but not tacrolimus, impairs glomerulo-tubular balance.
Absorption↗
The effect of colchicine on proximal tubular reabsorption.
Aquaporins, expressed in the brush border membrane (BB) could play a pivotal role in glomerulo-tubular balance (GTB) by effecting adaptive changes of water permeability to the variations in the load of filtered solutes. Since aquaporin expression is modulated by microtubule-dependent trafficking between endoplasmic reticulum and cell membranes, we used the microtubule poison colchicine to assess the importance of aquaporins in mediating GTB. The effects of colchicine 1.6x10(-4)m on proximal tubule volume reabsorption was tested on 48 nephrons of ten rats by micropuncture techniques. Thirty proximal tubules were sampled from the last proximal convolution before, and recollected during and again after the microinjection (MIJ), into the early proximal convolution or Bowman's space, of colchicine added to a Ringer solution. We studied 18 proximal tubules in the same way before, during and after the microperfusion (MP) of colchicine added to an ultrafiltrate of plasma into the peritubular capillaries. During MIJ, SNGFR did not change significantly from baseline (17.7+/-1.3 vs 20.9+/-1.8 nl min(-1), P>0.12). Post-control values were superimposable upon their paired pre-MIJ controls, when available (15.8+/-1.3 vs 13.5+/-1.5 nl min(-1), P>0.25). The measurements of percentage reabsorption (49+/-5 during baseline, 45+/-7 during MIJ, and 55+/-5 in post-control, P>0.6) and absolute reabsorption (8.1+/-0.7, 11.1+/-2. 2, and 7.9+/-1.3 nl min(-1), respectively, P>0.18) were also unchanged. The three average measurements obtained in control conditions, during MP and again in post-MP control were not significantly different for SNGFR (19.8+/-3.0, 20.0+/-4.7, and 20. 2+/-3.5 nl min(-1), P>0.48), percentage (55+/-3, 59+/-5, and 47+/-3%, P>0.35) and absolute reabsorptions (12.5+/-2.2, 12.4+/-4.6, and 9. 4+/-1.0 nl min(-1), respectively, P>0.42). MIJ and MP of vehicles were devoid of any measurable effect. Colchicine does not acutely affect volume reabsorption in the proximal tubule. Aquaporin trafficking, if any, is not involved in mediating glomerulotubular balance in the proximal tubule, although aquaporin expression and function could still be important, although regulated by mechanisms different from microtubule-dependent shuttling between endoplasmic reticulum and BB.
Absorption↗
Cyclosporine-A plus steroids versus steroids alone in the 12-month treatment of systemic lupus erythematosus.
The positive results obtained with cyclosporine-A both in an experimental model and in selected patients with advanced systemic lupus erythematosus support the hypothesis that the drug could be used as a steroid sparer in the earliest stages of active disease. To determine the 12-month clinical efficacy (disease control and steroid sparing), safety, and tolerability of low-dose cyclosporine-A plus steroids versus steroids alone, we designed a multicenter, open, prospective, randomized, pilot study, controlled for parallel groups. The patients were then followed up to month 24. A total of 18 consenting patients with recently diagnosed systemic lupus erythematosus of moderate severity indicated for the use of steroids in acute boluses and subsequently per os were enrolled at two university hospital medical centers. The protocol was based on three 1-g boluses of 6-methylprednisolone followed by cyclosporine-A (<5 mg/kg per day) plus prednisone 0.5-1 mg/kg per day per os, reduced by 5 mg/day every 2 weeks following clinical remission, versus the same doses of oral prednisone alone. The efficacy evaluation was based on a four-point scale (from absent/none to severe) for signs and symptoms of systemic lupus erythematosus and immunoserological parameters. The disease activity index and cumulative prednisone dose per patient were analyzed. Any adverse events were reported. All patients showed a reduction in disease activity index within the 1st month. The results were significantly better in the group with cyclosporine-A plus prednisone throughout month 12 (baseline and 12-month disease activity indexes: 21.3+/-8.6 and 5.0+/-2.5 versus 20.4+/-7.1 and 8.8+/-6.0 in the prednisone group, P<0.05). The 12-month cumulative mean dose of prednisone was significantly lower in the group with both cyclosporine-A plus prednisone (179.4+/-40.1 versus 231.8+/-97.1 mg/kg, P<0.005). No unusual adverse events related to the study drugs have been reported. In particular, renal function and blood pressure monitoring revealed no significant changes from mean baseline values in either group. No disease flares were reported in the group treated with cyclosporine-A plus prednisone during the 12- to 24-month period. Thus cyclosporine-A represents a useful corticosteroid sparer in the maintenance of clinical remission in patients with an early-stage, active systemic lupus erythematosus.
Adolescent↗
Dual effect of secretin on nephron filtration and proximal reabsorption depending on the route of administration.
Secretin is a vasoactive peptide capable of acting on transmembrane volume fluxes. We measured nephron filtration (SNGFR) and resorption during secretin microinjection (MIJ) into the tubular lumen or microperfusion (MP) into peritubular capillaries. In 24 rat nephrons, SNGFR, measured by collections from the distal tubule, rose from 25+/- 4 to 61+/-8 nl/min during MIJ of saline containing secretin 10(-9) M into the last convolution of the proximal tubule (LP). Percent and absolute resorptions rose from 70 to 90% and from 20+/-4 to 56+/-8 nl/min, respectively. During MIJ of secretin, 3 x 10(-)(9) M into the first convolution of the proximal tubule, SNGFR, measured at LP, rose from 32+/-4 to 61+/-8 nl/min, percent and absolute reabsorptions from 52+/-4 to 78+/-3% and from 16+/-2 to 50+/-7 nl/min, respectively (n = 30). During MP of secretin, 1.5x10(-9) M, SNGFR fell from 39+/-6 to 15+/-4, resorption from 19+/-4 to 9+/-2 nl/min, while percent resorption rose from 43+/-6 to 59+/-5% (n = 15). While all MIJ and MP changes were significant (P<0.001), paired pre- versus post-MIJ and MP values were not. Secretin is a powerful vasoconstrictor when perfused into peritubular capillary blood, unlike systemic and intra-arterial injections. When injected into the tubular lumen, it up-regulates SNGFR and increases reabsorption directly.
Animals↗
Scientific publications in gastroenterology and hepatology in Western Europe, USA and Japan in the years 1992-1996: a global survey.
AIM: To evaluate number and quality of publications in gastroenterology, hepatology and digestive endoscopy from Western Europe (Belgium, Denmark, France, Germany, Great Britain, Italy, the Netherlands, Spain, Sweden, Switzerland), Japan and USA over a recent 5-year period. METHODS: We screened by computer for full liver/gastrointestinal-related articles and reviews the top 40% of journals (according to the annual rating of the SCI Journal Citation Reports; Institute for Scientific Information database) in most clinical and basic science disciplines in the years 1992-1996. To be credited with an article, a given country had to be the site of the first institution where the work was conducted. Papers were rated according to the impact factor of the Institute for Scientific Information and to the ratio impact factor/mean European impact factor. Data were also normalized for nondefense research and development expenditure. RESULTS AND CONCLUSIONS: As randomly tested, the computer search had an error of +/- 5-10%. In Europe, Great Britain achieved the highest total impact factor and the highest number of papers. Most of the British impact factor came from publications in British journals. The total USA impact factor exceeded that of Europe by 20%. The average impact factor for a single paper was highest for the USA and, in Europe, for Germany. The temporal trend of total impact factor showed Spain improving by 9% per year, with Germany and Italy also displaying a substantial growth. Expressed per funds allocated in nondefense research and development, Great Britain and the USA had the highest cumulative impact factor.
Data Collection↗
Effect of endothelin 1 on proximal reabsorption and tubuloglomerular feedback.
Endothelin 1 (ET-1) is a powerful constrictor of the afferent glomerular artery, implicated in the occurrence of both functional and acute renal failure. Besides being produced by the endothelium, ET-1 is also secreted by proximal tubular cells, suggesting that it may act as an endoluminal messenger. The present study is intended to verify whether ET-1 may play a role in the tubuloglomerular feedback system. The experiments were performed in rat superficial glomeruli. In 25 nephrons we measured by the total collection technique the single-nephron glomerular filtration rate (SNGFR; nl/min) and reabsorption rates before (control) and during microinjection (MIJ) of ET-1 10(-7) M into the first proximal convolution or Bowman's space. The SNGFR rose from 27+/-3 to 61+/-11 nl/min (p<0.01), the percent proximal reabsorption rose from 43 to 74%, and the absolute reabsorption rose from 13+/-2 to 46+/-11 nl/min (p<0.01). In additional 23 nephrons the collections were performed at the earliest distal convolution accessible on the renal surface, while MIJ was performed in the last proximal convolution of the same nephrons. The SNGFR rose during MIJ from 22+/-3 to 40+/-6 nl/min (p<0.01), the percent reabsorption rose from 61 to 66% (p>0. 77), and the absolute reabsorption rose from 12+/-2 to 26+/-4 nl/min, (p<0.003). Exposure of the macula densa to intraluminally injected ET-1 causes an abrupt increase in SNGFR of the experimental nephron, in the absence of changes in systemic and renal hemodynamics. During proximal MIJ, ET-1 may have reached the macula densa during the time preceding the beginning of collection and interruption of the delivery of fluid to the distal nephron. ET-1 directly stimulates fractional and absolute volume reabsorption along the proximal tubule. Proximal secretion and/or filtration of ET-1 could represent a physiological mechanism to activate the tubuloglomerular feedback, eliciting a response opposite to that triggered by systemic and intrarenal infusion.
Animals↗
Iron deposition and progression of disease in chronic hepatitis C. Role of interface hepatitis, portal inflammation, and HFE missense mutations.
Histologically detectable iron (HDI) and HFE mutations were searched for in liver biopsy specimens from 58 Italian patients with chronic hepatitis C, and morphologic features were compared to examine their reciprocal relation and their contribution to disease progression. HDI was evident in 48% of cases with features of nonhemochromatosis iron overload. Total, sinusoidal, and portal HDI increased with stage; grade was related to all iron scores because of the contribution of portal inflammation and interface hepatitis. HFE mutations were seen in 47% of patients with chronic hepatitis C and in 28% of control subjects; they were related to stage and the His63Asp mutation to portal HDI. On multivariate analysis, grade but not stage or HFE mutations was associated with HDI in all sites. Interface hepatitis with its sequelae (sinusoidal capillarization and microshunting) represents a major factor in iron deposition in chronic hepatitis C and justifies the features of HDI. HFE mutations are not responsible for HDI deposition but could favor the progression of virus-induced damage independently from interference with iron metabolism.
Adolescent↗
Inadequate management of blood pressure in a hypertensive population.
Explore the source record for details and available documents.
Aged↗
Effect of eating on plasma radical-trapping antioxidant activity (TRAP) in patients with cirrhosis.
OBJECTIVES: To ascertain the effects of eating on plasma antioxidant capacity in patients with liver disease. DESIGN AND METHODS: Eighteen cirrhotic patients were compared to 18 age and sex-matched controls. TRAP was measured by a fluorometric assay after a 12 h fast, and 60, 120, and 180 min after the study participants had taken a drink formula food. RESULTS: In the fasting state, TRAP was higher in patients with alcoholic cirrhosis (847+/-39 micromol/L, mean +/- SEM) in comparison to patients with viral cirrhosis (653+/-41) and to controls (758+/-26) (p<0.005). In cirrhotic patients, TRAP did not change in the post-absorptive state. In controls, TRAP decreased progressively, to a value of 719+/-21 (p<0.02), and the AUC of the delta-values of TRAP and of plasma insulin showed an inverse correlation (r = -0.52, p<0.05). CONCLUSIONS: In normal subjects, but not in cirrhotics, TRAP decreases in the post-absorptive state, probably in relationship with the activation of metabolic pathways.
Antioxidants↗
Lipoprotein(a) and apolipoprotein(a) isoforms and proteinuria in patients with moderate renal failure.
BACKGROUND: Atherosclerotic diseases are a major cause of death in patients with renal failure. Increased serum concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases and have been demonstrated in patients with moderate renal failure, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. Variable alleles at the apolipoprotein(a) [apo(a)] gene locus are the main determinants of the serum Lp(a) level in the general population. The purpose of this study was to investigate apo(a) isoforms in patients with moderate renal failure and mild proteinuria (less than 1.0 g/day). METHODS: In 250 consecutive subjects recruited at a hypertension clinic, we assessed the renal function by 24-hour creatinine clearance, proteinuria, and microalbuminuria, as well as the prevalence of atherosclerotic disease, and we also measured apo(a) isoforms, serum albumin, and Lp(a) concentrations. RESULTS: Moderate impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) was found in 97 patients. Lp(a) levels were significantly greater in patients with moderate renal failure (21.7+/-23.9 mg/dl) as compared with patients with normal renal function (15.6+/-16.4 mg/dl, P<0.001), and an inverse correlation was observed between log Lp(a) and creatinine clearance (r = -0.181, P <0.01). However, no difference was found in the frequency of low molecular weight apo(a) isoforms between patients with normal (25.5%) and impaired (27.8%) renal function. Only patients with the smallest size apo(a) isoforms exhibited significantly elevated levels of Lp(a), whereas the large-size isoforms had similar concentrations in patients with normal and impaired renal function. No significant relationship was found between serum Lp(a) and proteinuria. Clinical and laboratory evidence of one or more events attributed to atherosclerosis was found in 9.8% of patients with normal renal function and 25.8% of patients with moderate renal failure (P<0.001). CONCLUSIONS: These results indicate that renal failure per se or other genes beside the apo(a) gene locus are responsible for the elevation of serum Lp(a) levels in patients with moderate impairment of renal function. The elevation of Lp(a) levels occurs independently of the level of proteinuria and may contribute to the risk for atherosclerotic disease in these patients.
Adult↗
Colorectal cancer screening in Italy: feasibility and cost-effectiveness in a model area.
OBJECTIVE: To evaluate the feasibility and cost-effectiveness of screening programmes for colorectal cancer in Italy. DESIGN; We compared five types of programmes: annual faecal occult blood testing, sigmoidoscopy (every 5 years), faecal occult blood testing plus sigmoidoscopy (every 1 and 5 years), colonoscopy (every 10 years) (all in the age group 55-69 years, last examination at 70 years) and 'filter' colonoscopy. The latter had to be performed in persons at 50 years of age and repeated every 10 years until the age of 70. Costs for the tests and colon cancer care were paid by the Regional Health Office to the hospitals performing the procedures/treatments. SETTING: Data were applied to a small model area in northern Italy (Gemona, 80,000 inhabitants) with well-known demographic (age distribution) and epidemiological (colon cancer incidence) features. RESULTS: All-inclusive 10-year costs per screenee and per death prevented (in US dollars) were: 965 and 77,200 for faecal occult blood testing; 436 and 15,500 for sigmoidoscopy; 1521 and 35,000 for sigmoidoscopy plus faecal occult blood testing; 510 and 15,100 for colonoscopy; 510 and 14,000 for 'filter' colonoscopy. With 'filter' colonoscopy the programme required 870 colonoscopies per year, while with colonoscopy 13,700 colonoscopies were needed at time zero. CONCLUSIONS: In Italy, screening programmes based on sigmoidoscopy/colonoscopy are more cost effective than those based on faecal occult blood testing. 'Filter' colonoscopy at age 50 appears superior to the other types of endoscopy-based screening programmes because it utilizes, at any point in time, a much smaller fraction of available resources.
Colonic Neoplasms↗
Post-infectious glomerulonephritis in a patient with Gemella haemolysans endocarditis.
Explore the source record for details and available documents.
Diagnosis, Differential↗
T cell receptor repertoire in B cell lymphoproliferative lesions in primary Sjögren's syndrome.
OBJECTIVE: Studies have analyzed T cell receptor (TCR)-Vbeta in benign, minor salivary or lacrimal gland, or kidney lesions in Sjögren's syndrome (SS). We investigated SS related lymphoproliferative lesions. METHODS: By "family" reverse transcriptase polymerase chain reaction, we studied the expression of 20 different TCR-Vbeta families in parotid lymphoproliferative lesions and peripheral blood lymphocytes (PBL) from 7 patients with primary SS, in PBL from 6 primary SS patients with no associated lymphoproliferative disorder, and in activated PBL from 2 healthy controls. T cell clonal expansion was investigated in 10 Vbeta families (i.e., the most expanded ones and those previously implicated in SS pathogenesis) by single strand conformation polymorphism (SSCP) analysis. Frozen sections from parotid gland specimens were tested by immunohistochemistry for the expansion of selected Vbeta families. Viral infection within the parotid lesions and serum autoantibody response were also studied. RESULTS: An unrestricted Vbeta pattern was observed. The most widely expressed Vbeta family in parotid lesions was Vbeta2, and Vbeta immunohistochemistry results were concordant with Vbeta mRNA findings. A similar pattern was observed in PBL, although the Vbeta2 family was expressed at lower levels. The parotid/PBL ratio was occasionally > 1.8-2.0 (indicative of local Vbeta overexpression) in different Vbeta families. T cell expansion proved to be largely polyclonal by SSCP analysis, and scattered T cell clonotypes were detected within different Vbeta families, with a different pattern from patient to patient. CONCLUSION: Our observations in SS related lymphoproliferative lesions largely reflect previous evidence in fully benign lesions. The pathogenetic events involved in autoimmune benign lesions in SS may then persist and play a role in SS related lymphoproliferative disorders. The link between the observed TCR-Vbeta repertoire and specific local triggering (auto)antigens remains to be elucidated.
Adult↗
Tubular reabsorption and sodium excretion during urine reinfusion.
BACKGROUND: The mechanisms responsible for the natriuresis that follows urine reinfusion was investigated in rats by clearance and micropuncture techniques. METHODS: In each animal two urine reinfusion periods (R1 and R2) were performed and compared to a non-urine-reinfusion, saline infusion period (S) sandwiched between them. RESULTS: Switching from urine reinfusion to an equivalent rate of saline loading was followed by a fall in Na excretion from 1.9 +/- 0.5 to 0.5 +/- 0.2% of filtered load, p < 0.002. Urine osmolality rose, and urine to plasma inulin concentration ratio rose significantly from 73 +/- 14 to 147 +/- 21 (p < 0.002). The changes in GFR, SNGFR, absolute and percent proximal reabsorption could not account for these findings. A reduced Na excretion coupled to increased urine osmolality indicates enhanced transport along a segment responsible for the urinary concentrating mechanism. Thus the data can be interpreted then as due to enhanced reabsorption along the ascending limb of Henle's loop. These changes were reversed by reinstituting urine reinfusion after the S period. The consensual changes in Na+ and K+ excretion excluded an effect of urine reinfusion on the distal exchange site. There was a continuous fall in proximal reabsorption from R1 (76 +/- 3%) to S (69 +/- 3%) to R2 (62 +/- 5%) which was inversely correlated with the changes in hematocrit (R = 0.49, p < 0.026). This indicates that part of the late diuresis and natriuresis was due to volume expansion. An osmotic effect of reinfused urine solutes was suggested by a late rise in plasma osmolality, from 312 +/- 13 to 323 +/- 8 mOsm/kg. Osmotic diuresis could have exerted additive effects upon those of volume expansion, accounting for the late fall in proximal reabsorption. CONCLUSIONS: We conclude that the acute effects of urine reinfusion are due to changes in transport of solutes and permeability to water along distal tubular segments. The changes in plasma osmolality during the last period of the present acute experiments, suggest the possibility that solute retention may be linked to the chronic effects of urine reinfusion.
Animals↗
Increased serum lipoprotein(a) levels in patients with early renal failure.
BACKGROUND: Elevated serum lipoprotein(a) levels have been found in patients with end-stage renal disease and in patients undergoing dialysis, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. It is not known whether lipoprotein(a) levels are elevated in the early phases of renal disease. OBJECTIVE: To evaluate levels of lipoprotein(a) and other lipids and the prevalence of atherosclerotic disease in patients with early renal failure. DESIGN: Cross-sectional study. SETTING: Hypertension clinic of a university medical center. PATIENTS: 257 patients with normal renal function and 160 patients with early impairment of renal function (creatinine clearance, 30 to 89 mL/min per 1.73 m2 of body surface area). MEASUREMENTS: Renal function was assessed by 24-hour creatinine clearance, proteinuria, and microalbuminuria. Cardiovascular disease status was also assessed. Serum lipoprotein(a), lipids, apolipoproteins, and apolipoprotein(a) isoforms were measured. RESULTS: Age, blood pressure, and serum lipoprotein(a) levels were greater in patients with early renal failure than in those with normal renal function and were independently associated with the presence of decreased creatinine clearance. Serum lipoprotein(a) and creatinine clearance were inversely correlated. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was greater in patients with early renal failure than in those with normal renal function. The frequency distribution of apolipoprotein(a) isoforms was similar in patients with normal and those with impaired renal function. CONCLUSIONS: Serum lipoprotein(a) levels are elevated in patients with early impairment of renal function and are associated with greater prevalence of cardiovascular disease. An inverse correlation between serum lipoprotein(a) level and creatinine clearance and a frequency distribution of apolipoprotein(a) isoforms similar to that of normal patients point to decreased renal catabolism as a probable mechanism of lipoprotein(a) elevation in patients with early renal failure.
Adult↗
The site of action of furosemide.
To establish whether furosemide (F) acts on the proximal tubule beside the thick ascending limb of Henle's loop, we reviewed the data from 55 rats studied before and during the i.v. infusion of 10 mg kg-1 of furosemide. These animals were the object of previously published studies. SNGFR was 42.6+/-1.1 nl min-1 during baseline conditions (B), 42.7 nl min-1 during F (P>0.9). In 151 paired last proximal tubular samples, percentage reabsorption was 71.72 before and 71.72% after F (P=1.0). In 64 paired early distal tubular samples, percent reabsorption fell from 86% in B to 78% during F (P<0.0001). During F, the urine flow rate expressed as a percentage of GFR (24+/-2%) was significantly correlated (R=0.52, P<0.0001) with the percent delivery of filtrate out of the proximal tubule (26+/-3%). These data demonstrate that, even at this very high dosage, F does not act on the proximal tubule. It inhibits transport on the ascending limb of Henle's loop. By allowing the delivery of isotonic tubular fluid to the distal tubule, it causes a fall in volume absorption along the early distal convolution in proportion to its baseline water permeability. It increases urine flow by abolishing the interstitial hypertonicity and, consequently, the osmotically driven solvent flow across the distal epithelium and collecting ducts. Therefore the urine flow rate during F closely approximates volume delivery out of the proximal tubule.
Animals↗