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Biomedical subjects

H O Senekjian

Publications and source records attributed to H O Senekjian.

At least 19 recordsLinked to original sources
PubMed1996

Reducing symptoms during hemodialysis by continuously monitoring the hematocrit.

Previous studies have demonstrated that patients on hemodialysis develop intradialytic symptoms when the blood volume decreases to a critical level. Using a continuous monitor (CRIT-LINE; In-Line Diagnostics, Riverdale, UT) to determine the instantaneous hematocrit and blood volume, we observed that certain intradialytic symptoms occurred at a patient-specific hematocrit. In the present study, we exploited this hematocrit threshold concept to decrease the occurrence of lightheadedness, cramping, and nausea, regardless of blood pressure changes. In the first phase of the study, hematocrit threshold was established in six hypotension-prone patients. Five patients entered into the second phase in which ultrafiltration rates were increased 25 percent above prescribed values at the beginning of the experimental sessions. Subsequently during the experimental sessions, ultrafiltration rates were manipulated to maintain the instantaneous hematocrit value 2 units below the established hematocrit threshold. Sessions without ultrafiltration rate adjustments based on hematocrit served as controls. There were no differences between experimental (n = 27) and control (n = 28) sessions with respect to treatment time (230 minutes v 229 minutes), fluid volume removed (3,351 mL v 3,383 mL), and maximum percentage change in systemic blood pressure (-26 percent v -24 percent). However, there were less symptoms during the experimental sessions (26 percent v 57 percent; P = 0.038). These data suggest that a twofold reduction in intradialytic symptoms can be achieved using continuous hematocrit monitoring without altering treatment times or volume removed in hypotension-prone patients.

Blood Volume↗
PubMed1991

Prescribing hemodialysis using a weekly urea mass balance model.

Prescribing hemodialysis by monitoring only predialysis BUN concentrations is not sufficient to guarantee adequate therapy. Results from the National Cooperative Dialysis Study have suggested that hemodialysis therapy is adequate if the protein catabolic rate is maintained greater than 1 g/day/kg body weight and simultaneously if sufficient hemodialysis is prescribed to maintain either a time-averaged BUN concentration (TACurea) less than 50 mg/dl or a value of Kt/V greater than unity. In the present study mathematical relationships were derived from a weekly urea mass balance model that permit an evaluation of TACurea and of protein catabolism via the urea generation rate (G) without the need for conventional urea kinetic modeling. The parameters TACurea and G were simply calculated from a midweek predialysis BUN concentration (BUNMW) by: TACurea = 0.7 BUNMW G = 0.7 BUNMW(Kr + Kd tau/T) where Kr, Kd, tau and T denote residual renal urea clearance, dialyzer urea clearance, number of minutes of hemodialysis per week, and number of minutes total in a week, respectively. Clinical results from 139 modeling sessions on 91 patients demonstrated that TACurea and G derived from urea kinetic modeling correlated highly with those calculated from the above equations (r = 0.96 and 0.94, respectively). It is concluded that individualized hemodialysis prescription and adequacy of therapy can be assessed by monitoring TACurea and G by calculation from a weekly urea mass balance model.

Adult↗
PubMed1985

Microinjection study of renal calcium absorption in the phosphate-depleted rat.

Tracer microinjection studies were performed in chronically phosphate-depleted (CPD) and phosphate-supplemented (PS) rats in order to determine the site of the defect in calcium absorption which developed in CPD. Calcium recovery in the final urine was significantly higher in CPD than in PS rats after microinjections into the early and the late proximal tubules. However, there was no significant difference in the urinary recovery between the two groups after injection into the early and late distal convoluted tubules. The difference in calcium recovery in late proximal studies persisted during PTH infusion. This indicates that there is a defect in calcium absorption in phosphate-depleted rats between late proximal and early distal tubules, which is not correctable with PTH infusion.

Animals↗
PubMed1984

Hemodialysis of doxepin and desmethyldoxepin in uremic patients.

The disposition of doxepin and its active metabolite desmethyldoxepin was investigated in five uremic patients undergoing hemodialysis. The hemodialysis system yielded a mean extraction efficiency of 7.6% for doxepin and 13.9% for desmethyldoxepin. Mean dialysis clearances were 10.8 and 18.1 ml/min for doxepin and desmethyldoxepin, respectively. The drug and metabolite recovery constituted a very small fraction of the body store, i.e., less than 1%. Hemodialysis did not significantly alter the plasma half-life of doxepin, 14.6 +/- 4.3 h, or of desmethyldoxepin, 25.4 +/- 5.5 h. The nondialyzability of both compounds could be attributed to the compounds' protein binding and volume of distribution. The dialysis experiments show that modification of the usual dosage regimen is not necessary during hemodialysis or on dialysis days. The dialysis parameters confirm that hemodialysis is not likely to be of value in the management of acute doxepin poisoning.

Adult↗
PubMed1984

IgA nephropathy in a patient with ankylosing spondylitis and a solitary kidney.

We describe a patient with ankylosing spondylitis and psoriasis who was found to have IgA nephropathy in a solitary kidney. Renal biopsy demonstrated mesangial proliferation and interstitial nephritis with mesangial deposition of IgA. Although the renal disease and the rheumatic disease could have been present together by chance association, evidence is presented to suggest a possible common pathogenesis.

Glomerulonephritis↗
PubMed1983

Efficacy of intravenous vancomycin in the treatment of gram-positive peritonitis in long-term peritoneal dialysis.

Peritonitis is the major complication of long-term peritoneal dialysis. Gram-positive bacteria are responsible for two thirds of the total number of peritonitis episodes. Conventional therapy consists of daily administration of antibiotics, either parenterally or intraperitoneally. Vancomycin, an antibiotic with a prolonged half-life in renal failure, has a wide spectrum of activity against gram-positive bacteria and diffuses readily across the peritoneal membrane. In the present study, 82 percent of gram-positive peritonitis episodes were cured following the intravenous administration of vancomycin at weekly intervals. This cure rate compares favorably with that obtained following conventional therapy of peritonitis. It is concluded that intravenous vancomycin is an effective treatment for gram-positive peritonitis in patients undergoing long-term peritoneal dialysis. This form of therapy is convenient, reduces hospitalization, minimizes cost, and avoids possible contamination of the peritoneal dialysate used during the intraperitoneal administration of antibiotics.

Bacteria↗
PubMed1983

Maleic acid-induced reabsorptive dysfunction in the proximal and distal nephron.

Micropuncture and clearance studies were performed to assess reabsorptive function in the proximal and distal nephron of rats with experimental Fanconi's syndrome induced by maleic acid. Anesthetized rats were studied by free-flow micropuncture of the late proximal tubule 90-120 min after continuous intravenous administration of maleic acid, 100 mg X kg-1 X h-1. Compared with control rats, the reabsorption of sodium and phosphate was significantly reduced (P less than 0.001 and less than 0.02, respectively). Tubular fluid-to-ultrafiltrate (TF/UF) chloride concentration ratio was 1.00 +/- 0.02 compared with 1.16 +/- 0.03 (P less than 0.01) in controls, suggesting a nearly total inhibition of proximal bicarbonate reabsorption. Whole kidney fractional excretions of sodium and chloride were increased significantly (P less than 0.02) but could not be explained by enhanced delivery of these solutes out of the late proximal tubule. To assess whether distal nephron reabsorption of sodium and chloride were inhibited by maleic acid, clearance studies were performed during water diuresis in awake rats. During maleic acid administration, 200 mg X kg-1 X h-1, urine flow rate (P less than 0.02) and the fractional excretions of sodium and chloride (P less than 0.001) increased significantly, but fractional free water clearance decreased from 7.16 +/- 0.42 to 4.03 +/- 0.68% (P less than 0.001). In acetazolamide-treated control rats but not in maleic acid-treated rats with similar bicarbonaturia, the magnitude of fractional free water clearance closely approximated the simultaneously measured fractional distal delivery of chloride. These studies suggest that maleic acid inhibits reabsorption at a distal nephron site or sites as well as in the proximal tubule.

Absorption↗
PubMed1983

Modulation of the hydro-osmotic effect of vasopressin on the rabbit cortical collecting tubule by adrenergic agents.

The effects of catecholamines on antidiuretic hormone ([Arg(8)]-vasopressin [AVP])-induced water absorption were evaluated in cortical collecting tubules isolated from the rabbit kidney and perfused in vitro. In the presence of AVP (100 muU/ml), net fluid volume absorption (J(v), nanoliters per minute per millimeter) was 1.14+/-0.12 and osmotic water permeability coefficient (P(f), X 10(-4) centimeters per second) was 217.3+/-39.9. The addition of the alpha-adrenergic agonist, phenylephrine (PE), in a concentration of 10(-6) M resulted in a significant decrease in J(v) and P(f) to 0.83+/-0.13 (P < 0.001) and 148.8+/-41.8 (P < 0.02), respectively. Increasing the concentration of PE to 10(-5) M resulted in a further decrease in J(v) and P(f) to 0.53+/-0.05 (P < 0.05 vs. PE 10(-6) M) and 88.5+/-9.0 (P 0.05 vs. PE 10(-6) M), respectively. In a separate group of tubules, in the presence of AVP (100 muU/ml) and PE (10(-5) M), J(v) and P(f) were 0.35+/-0.07 and 66.0+/-17.3, respectively. The addition of the alpha-adrenergic antagonist, phentolamine (PH), in a concentration of 10(-6) M resulted in a significant increase in J(v) to 1.07+/-0.19 (P < 0.001) and P(f) to 193.3+/-35.9 (P < 0.005). PH (10(-5) M) alone did not significantly affect J(v) and P(f) in the presence of AVP (100 muU/ml) nor in the presence of 8-bromo adenosine 3',5' cyclic monophosphate (8-BrcAMP). J(v) and P(f) were 1.20+/-0.21 and 174.0+/-25.8, respectively, in the presence of 8-BrcAMP (10(-4) M). We next examined the effect of the beta-adrenergic agonist, isoproterenol (ISO), on J(v) and P(f) in the presence of AVP. J(v) and P(f) were 1.04+/-0.10 and 202.6+/-17.2, respectively, in the presence of AVP (100 muU/ml) and 1.06+/-0.18 and 193.4+/-27.7, respectively, in the presence of AVP (10muU/ml). However, in the presence of AVP in a concentration of 2.5 muU/ml, J(v) was 0.60+/-0.07 and P(f) was 100.7+/-24.7. ISO (10(-6) and 10(-5) M) did not have any significant effect in the presence of the above maximal and submaximal concentrations of AVP. In the absence of AVP, control J(v) was 0.01+/-0.12 and P(f) was 4.6+/-11.0. The addition of ISO at 25 or 37 degrees C did not result in any significant change in J(v) or P(f). These studies indicate that alpha-adrenergic agonists directly inhibit AVP-mediated water absorption at the level of the tubule, an effect that can be blocked by a specific alpha-adrenergic antagonist. This effect appears to be exerted at the level of activation of adenylate cyclase since it is absent in the presence of cAMP. The beta-adrenergic agonists do not directly inhibit or enhance AVP-mediated water absorption at the level of the renal tubule.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Water absorption in the proximal tubule: effect of bicarbonate, chloride gradient, and organic solutes.

Simultaneous in vivo capillary and luminal microperfusion studies were performed in the superficial proximal convoluted tubule of the rat to determine the effect of intraluminal bicarbonate, the imposition of a transepithelial chloride gradient, and the addition of organic solutes to the luminal perfusion solution on the rates of water absorption (Jv). The capillary perfusion solution contained NaCl, NaHCO3, and KCl. Perfusion of both capillary and lumen with the same solution resulted in a Jv of 3.01 +/- 0.24 nl/min/mm. Imposition of a transepithelial chloride gradient (equimolar substitution of NaCl for NaHCO3 in the luminal solution) resulted in a Jv of 3.18 +/- 0.21 nl/min/mm (P = NS). Addition of cyanide to both solutions in the presence of a chloride gradient resulted in a significantly lower Jv of 2.21 +/- 0.19 nl/min/mm. Luminal substitution of Na cyclamate for NaHCO3 resulted in a solution containing no bicarbonate and no chloride gradient. Jv averaged 0.34 +/- 0.08 nl/min/mm. Addition of cyanide to the solution totally inhibited Jv. The addition of D-glucose, L-alanine, or both, to luminal solutions containing bicarbonate or in the presence of a chloride gradient did not significantly affect Jv. Addition of both organic solutes to the NaCl-Na cyclamate luminal solution resulted in a significantly higher Jv of 0.77 +/- 0.14 nl/min/mm. These studies indicate that Jv in the rat superficial proximal tubule is influenced by active sodium transport, by the presence of bicarbonate in the lumen, and/or by the imposition of a transepithelial chloride gradient. The organic solutes D-glucose and L-alanine also influence water absorption, but this effect could only be demonstrated under some experimental conditions.

Animals↗
PubMed1983

Protective effect of oral clonidine in the prophylaxis and therapy of mercuric chloride--induced acute renal failure in the rat.

Previous studies have demonstrated that the sympathomimetic agent clonidine, administered intravenously immediately prior to injury, provides partial protection against the acute structural and functional impairments associated with experimental ischemic and nephrotoxic ARF. To determine the effect of clonidine, administered orally, on the prolonged course of HgCl2-induced ARF, two groups of rats were studied for a period of 5 days after injury. For 5 days before HgCl2 administration (2 mg/kg s.c.) and throughout the study group I drank water while group II had clonidine (5 mg/L) added to water. The fatality rate was 77% in group I as compared to 11% in group II (p less than 0.001). Renal function (CCr and FENa) was better preserved and recovered more rapidly in group II rats protected with clonidine. Both groups showed varying degrees of proximal tubular cell injury, but group II had significantly fewer necrotic cells and demonstrated earlier evidence of regeneration. Whereas none of the injured cells in the clonidine-pretreated group revealed evidence of calcification, on the second day half the cells of the pars recta in the outer stripe of the medulla were calcified in group I. In group III animals, oral clonidine was started 2 hr after the injection of HgCl2 and also resulted in a significant reduction in fatality rate from 40% in control group to 0% in the clonidine-treated group. In addition, CCr and FENa were better preserved and recovered more rapidly in this group of clonidine-treated rats. These results indicate that oral clonidine, administered either before or shortly after HgCl2-induced ARF, exerts a salutory effect on the course and mortality of ARF by providing protection of renal function and enhancement of the recovery process.

Acute Kidney Injury↗
PubMed1983

Absorption and disposition of ibuprofen in hemodialyzed uremic patients.

The absorption and disposition of ibuprofen was investigated in seven hemodialyzed uremic patients. Ibuprofen (400 mg) was orally administered to each patient 1 hr or 4 hr prior to hemodialysis. Uremic patients appeared to absorb ibuprofen at a slower rate as compared to normal subjects. The hemodialysis systems used in this study yielded a mean extraction efficiency of 16.7% for ibuprofen, with a mean dialysis plasma clearance of 22.7 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the ingested dose of ibuprofen (less than 4%). The half-life of ibuprofen (1.3-1.9 hr) was not significantly altered by hemodialysis. Observations of extraction efficiency, drug recovery and half-life during dialysis suggested nondialyzability of ibuprofen, probably due to its extensive protein binding (approximately 90%). Uremic patients may require a comparatively longer time to achieve the therapeutic concentration attained in normal volunteers. However, dosage adjustment is not required once a regimen is implemented in uremia.

Absorption↗
PubMed1982

Alpha and beta adrenergic agonists stimulate water absorption in the rat proximal tubule.

Simultaneous capillary and luminal microperfusion studies were performed in the rat proximal tubule to determine the effects of the beta agonist isoproterenol and the alpha agonist phenylephrine on water absorption. Capillary and luminal perfusion solutions were composed such that organic solutes were not present, no bicarbonate was present in the lumen, and no chloride gradient was imposed. Under such conditions, water absorption (Jv) averaged 0.36 +/- 0.11 nl . min-1 . mm-1. the addition of isoproterenol to the capillary solution in concentrations of 10(-6) and 10(-4) M resulted in significantly higher Jv's of 0.68 +/- 0.10 and 0.71 +/- 0.11 nl . min-1 . mm-1, respectively. The enhancing effect of isoproterenol was inhibited by the beta blocker propranolol (10(-4) M), but not by the alpha blocker phentolamine (10(-7) M). The addition of phenylephrine (10(-6) M) to the capillary perfusion solution also resulted in a significantly higher Jv of 0.84 +/- 0.14 nl . min-1, an effect inhibited by phentolamine (10(-7) M), but not by propranolol (10(-4) M). Neither phentolamine nor propranolol alone in the concentrations indicated had an effect on water absorption. These experiments indicate that both alpha and beta agonists stimulate water absorption in the superficial proximal tubule of the rat. This effect appears to be relatively specific for each class of agonist, as demonstrated by the effects of the specific antagonists.

Adrenergic alpha-Agonists↗
PubMed1982

Oxalate transport by proximal tubule of the rabbit kidney.

Oxalate transport was examined in isolated perfused segments of the proximal tubule of the rabbit. When oxalate was present in a concentration of 10(-5) M in the bathing and perfusing solutions, there was a net secretory flux of oxalate of 36.4 +/- 1.4, 34.7 +/- 4.3, and 20.7 +/- 2.8 x 10(-15) mol . min-1 . mm-1 in the superficial S1, S2, and S3 segments, respectively, at a bath temperature of 37 degrees C. The net secretory flux of oxalate in the juxtamedullary S1 and S2 segments was 12.8 +/- 2.5 and 12.5 +/- 3.6 x 10(-15) mol . min-1 . mm-1, respectively. Cooling to 25 degrees C resulted in a significant decrease in the net flux of oxalate. When oxalate was present in the bathing solution only (10(-5) M), the bath-to-lumen flux of oxalate was not different from the net flux in the superficial and juxtamedullary S2 segments. These studies demonstrate that oxalate undergoes net secretion in the rabbit proximal tubule. This occurs against an electrical gradient, in the absence of concentration gradients, and can be inhibited by cooling, suggesting an active transport process. There is significant internephronal heterogeneity in the proximal tubule for oxalate secretion.

Animals↗
PubMed1982

Vesicoureteral reflux and reflux nephropathy.

Vesicoureteral reflux is an anatomic abnormality, mostly affecting a pediatric population, which may be the second leading cause of end-stage renal failure. Most cases of reflux are due to abnormalities in the insertion of the ureters into the bladder, either congenital or acquired. Most commonly, VUR is discovered during routine evaluation of urinary tract infections, but may also be present in patients with severe hypertension or chronic renal failure. The diagnosis is confirmed radiologically, utilizing either voiding cinecystography or radioisotopic methods. VUR can result in renal failure through scarring secondary to 'chronic pyelonephritis' or through a glomerulopathy, possibly immune in origin. In most series, the glomerulopathy is felt to be the cause of the end-stage renal failure. Treatment of VUR includes conservative (medical) management with the hope that maturation of the ureterovesical junction will cure reflux. Surgical therapy is reserved for those patients in whom this maturation is not expected to occur or in those whose urinary infections cannot be controlled. In those patients who have developed the glomerulopathy secondary to VUR, surgery may not halt the progression of the renal disease. VUR in a transplanted kidney may result in a higher risk of loss of the graft due to glomerulopathy or chronic rejection.

Adolescent↗
PubMed1982

Pseudomonas peritonitis and continuous ambulatory peritoneal dialysis.

In a population of 44 patients receiving continuous ambulatory peritoneal dialysis (CAPD) for a total of 591 patient months, there were 104 episodes of peritonitis. The organisms were gram-positive in 65.4%, gram-negative in 23.1%, and cultures of the dialysate were sterile in 11.5%. Pseudomonas aeruginosa was the most frequently encountered gram-negative organism, accounting for 38.5% of the gram-negative infections or 9.6% of all infections. In all cases of P aeruginosa peritonitis, aminoglycoside antibiotic therapy for up to four weeks failed to eradicate the infection, and all patients required removal of the Tenckhoff catheter because of the presence of a sinus tract infection. We conclude that P aeruginosa is the most frequent cause of gram-negative peritonitis in patients receiving CAPD. The presence of a sinus tract infection should be suspected in all patients in whom peritonitis secondary to this organism develops. Removal of the Tenckhoff catheter will be required to cure the peritoneal infection.

Adult↗
PubMed1982

Free-flow micropuncture study of renal urate transport in the Munich-Wistar rat.

In order to determine the nephron sites of urate reabsorption, the fractional rates of delivery of urate to specific segments of the superficial and deep nephrons were determined by the free-flow micropuncture technique in the Munich-Wistar rat. In nondiuretic control animals, the fractional delivery of urate to the late proximal tubule (34.1 +/- 3.6%), distal tubule (39.0 +/- 6.2%), base (32.6 +/- 3.2%), and tip (32.3 +/- 5.6%) of the papillary collecting duct were not different from one another. In animals in which the extracellular fluid volume was expanded with isotonic saline and in animals infused with the uricosuric diuretic MK-196, the fractional rates of urate delivery to any given nephron segment were significantly higher than in controls. There were no significant differences in either group, however, in the rates of delivery of urate to the specific nephron sites sampled. These studies indicate that urate absorption occurs primarily in the proximal convoluted tubule, but provide no evidence for nephron heterogeneity for urate transport. Expansion of the extracellular fluid volume and the infusion of MK-196 resulted in a higher fractional excretion of urate.

Absorption↗