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Biomedical subjects

R M Hakim

Publications and source records attributed to R M Hakim.

At least 91 records · Page 5Linked to original sources
PubMed1989

Progression of chronic renal failure.

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.

Creatine↗
PubMed1989

Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients.

A sub-set of patients on chronic hemodialysis develop sustained hypotension (systolic pressure less than 100 mm Hg). To determine whether this hypotension could be due to altered production of, or sensitivity to angiotensin II (AII), we measured plasma renin (PRA), AII, and aldosterone in nine hypotensive and nine normotensive dialysis patients; we also assessed their sensitivity to infused AII and studied AII binding to their platelets as an indicator of AII receptors on vascular smooth muscle. All studies were performed just before dialysis when subjects were relatively volume-expanded. Hypotensives had higher PRA (5.7 +/- 2.4 vs. 2.1 +/- 0.8 ng AI/ml/hr, P less than 0.05). AII (56 +/- 15 vs. 31 +/- 3 pg/ml), and aldosterone (91 +/- 35 vs. 21 +/- 7 ng/dl, P less than 0.05) than did normotensives. During AII infusion at 1, 3, 10, and 30 ng/kg/min for 15 minutes each, hypotensives displayed a significantly blunted pressor effect across the range of AII doses. In parallel with this, hypotensives showed reduced AII receptors on their platelets compared to normotensives (0.8 +/- 0.4 vs. 3.6 +/- 1.0% 125I-AII specifically bound; P less than 0.03). Binding analysis revealed a single affinity state for the AII receptors which was similar in both groups (Kd = 3.2 +/- 1.1 for hypotensives vs. 3.8 +/- 0.7 x 10(-10) M for normotensives). The two groups had similar levels of plasma catecholamines, similar slowing of heart rate during AII infusion and no postural hypotension, indicating intact sympathetic nervous system pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Kinetics and efficacy of deferoxamine in iron-overloaded hemodialysis patients.

We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron-overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half-life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe-feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron-overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes.

Adult↗
PubMed1988

Biochemical parameters in chronic renal failure.

We analyzed biochemical data derived from 911 patients with renal insufficiency observed at our institution for periods up to 7 years. During early renal failure (RF) (creatinine less than 5 mg/dL), the rate of change of hematocrit, total CO2 (tCO2) and urea per unit change of creatinine was significantly higher than during moderate (creatinine between 5 and 10 mg/dL) or advanced (creatinine greater than 10 mg/dL) RF. For example, the rate of change of hematocrit (%, volume/volume [v/v]) was (mean +/- SEM) -2.15 +/- 0.15% for each 1 mg/dL increase in creatinine in the range of creatinine less than 5 mg/dL, whereas for the range of creatinine greater than 10 mg/dL, the rate of change was only -0.48 +/- 0.06% (P less than 0.001). Similarly, the rate of change of tCO2 was -1.68 +/- 0.09 mEq/L for each 1 mg/dL increment in creatinine concentration during early RF, and -0.19 +/- 0.09 mEq/L per unit increase in creatinine during advanced RF (P less than 0.001). Chloride concentration initially increased as a function of creatinine in early RF, but decreased in advanced RF, whereas the anion gap increased throughout the course of RF. Mean serum phosphate concentration also increased steadily, but remained below the upper range of normal (4.7 mg/dL) during early RF without the use of phosphate binders. These data suggest that different biochemical parameters change at different rates as a function of the severity of renal dysfunction, and that although phosphate retention may occur, hyperphosphatemia is not a hallmark of early RF.

Acid-Base Equilibrium↗
PubMed1987

Iron overload and mobilization in long-term hemodialysis patients.

Iron overload from repeated transfusions of RBCs in long-term hemodialysis patients is a problem of increasing clinical significance. We report on the prevalence of and diagnostic criteria for identification of hemodialysis patients with iron overload. In 150 unselected hemodialysis patients, 62 (41%) had ferritin levels greater than 2,000 ng/mL (normal = 10 to 360 ng/mL). In 16 of these patients, accurate transfusion histories were obtained and ferritin levels correlated with calculated transfusional iron burden (r = 0.553, P less than .05). These patients could be divided into two distinct groups on the basis of their response to a single dose (2 g, IV) of deferoxamine: "high" responders had twice the level of feroxamine (the chelated product of deferoxamine and iron) of the "low" responders (P less than .001). High responders also had significantly higher prevalence of the "hemochromatosis" alleles A3, B7, and B14 than a large group of dialysis patients awaiting transplantation (71% v 37%, P less than .001). In two patients with iron overload and clinically significant bone disease, bone histology revealed prominent iron staining at the calcification front. We conclude that transfusional iron overload is a significant clinical problem in long-term hemodialysis patients, that may also be associated with bone pathology.

Adult↗
PubMed1986

Clinical sequelae of complement activation in hemodialysis.

During clinical hemodialysis, interactions between blood and dialysis membranes lead to the activation of several pathways such as the coagulation, kallikrein and complement pathways. The sum of these interactions defines the biocompatibility of the dialysis membrane; Cuprophane membranes, the most widely used dialysis membranes elicit intense blood-membrane interactions. Complement activation can be measured by determining the concentration of the activated third and fifth component of the complement cascade, namely C3a and C5a. These active products lead to the well known neutropenia seen during the early phase of dialysis. However, the neutropenia is only the most visible manifestation of the effects of complement activation. C5a-induced secretion of granule enzymes from neutrophils and their subsequent desensitization to further chemotaxis and phagocytosis may be an important factor in the incidence of infections in the dialysis patient. Endothelial cell damage by complement stimulated granulocytes mediated via superoxide anion may also play a role in the pulmonary dysfunction seen in dialysis patients, and recent evidence suggests that complement products may lead to cardiac dysfunction manifested by impaired ventricular contractility. Although some of these events may not be mediated directly by activated complement products, recent studies suggest that they play a role in the activation of several other pathways and pathophysiological process.

Biocompatible Materials↗
PubMed1985

Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis.

To identify the mechanisms accounting for hemodialysis-induced granulocytopenia, we undertook quantitative kinetic studies of a granulocyte-adhesion-promoting surface glycoprotein (Mo1). In eight patients undergoing maintenance hemodialysis, there was a fivefold increase in the mean cell-surface expression of Mo1 within 15 minutes after the start of dialysis with a new cuprophane membrane. The peak increase in surface Mo1 coincided with the maximal drop in neutrophil count and with the peak rise in the plasma levels of the complement-activation products C5a desArg and C3a desArg. During dialysis on a membrane being reused for the fifth time, no significant complement activation, no increase in Mo1 expression, and no change in neutrophil count were seen. C5a desArg (but not C3a desArg) induced a comparable increase in Mo1 expression on normal granulocytes in vitro at concentrations similar to those measured in vivo. Chemotactic peptide-induced granulocyte aggregation (a reflection of increased cell-to-cell adhesiveness) was specifically blocked by mouse monoclonal antibodies to Mo1 in vitro. These data suggest that the increased expression of Mo1 on granulocytes in vivo is in part mediated by C5a (and C5a desArg). The quantitative increase in granulocyte-surface Mo1 may provide a mechanism for initiating leukoaggregation, sequestration of granulocytes, and neutropenia during hemodialysis.

Adult↗
PubMed1985

Hemodialysis-associated platelet activation and thrombocytopenia.

The interactions between platelets and dialysis membranes were studied prospectively in 10 patients undergoing long-term stable dialysis. Transient but significant thrombocytopenia and platelet activation were found during dialysis with the commonly used cuprophane membrane. Platelet counts decreased from 231 +/- 21 X 10(3)/mm3 before dialysis to 127 +/- 28 X 10(3)/mm3 at 90 minutes following initiation of dialysis (p less than or equal to 0.007). Thromboxane B2, an index of platelet activation, also increased from a baseline level of 1.06 +/- 0.2 pg/10(6) platelets to 7.3 +/- 3.0 pg/10(6) platelets at 90 minutes (p less than or equal to 0.04). Cuprophane membranes were also shown to induce complement activation with C3a desArg, the stable derivative of C3 activation, showing a threefold increase from baseline 15 minutes after initiation of dialysis. In contrast, during dialysis with a non-complement-activating dialyzer membrane, polymethylmethacrylate, thrombocytopenia and platelet activation were not observed. These data suggest that platelet activation and thrombocytopenia during hemodialysis are associated with complement activation during hemodialysis in a manner similar to dialysis-associated neutropenia.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis.

We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required.

Acute Kidney Injury↗
PubMed1985

Effects of acetate and bicarbonate dialysate in stable chronic dialysis patients.

The effects of acetate and bicarbonate dialysate on the biochemical and clinical parameters of 16 stable chronic hemodialysis patients were investigated in a double-blind crossover study. A central delivery system was used for both types of dialysates with identical sodium concentrations (138 mEq/liter) and osmolality in a single-pass dialysate flow. The results indicate that dialysis with bicarbonate leads to significantly less hypoxemia (P less than or equal to 0.001) and hypotensive episodes (P less than or equal to 0.002) than with acetate. Pre- to post-dialysis blood pressure changes were also more marked during acetate dialysis. Older patients with recurrent hypotension on acetate benefit most from bicarbonate dialysate. This group of patients appears to metabolize acetate more slowly and has a significantly lower post-dialysis bicarbonate concentration (P less than or equal to 0.005) than asymptomatic patients during dialysis with acetate dialysate.

Acetates↗
PubMed1985

Formaldehyde kinetics and bacteriology in dialyzers.

The kinetics of formaldehyde washout in new and reused dialyzers with 2% (w/v) and 4% formaldehyde solution was studied. Using a standard method of rinsing, the concentration of formaldehyde decreases exponentially, but the rate of decrease and the steady-state level depends on the type of dialyzer. The residual quantity of formaldehyde using a 4% solution is more than twice that seen with a 2% solution in similar dialyzers. Bacteriological tests on water-adapted, formaldehyde-resistant organisms indicate that a significant proportion of these organisms can survive a 4-hr incubation with 4% formaldehyde at 20 degrees C. However, increasing the temperature of incubation to 40 degrees C or the addition of ethanol up to 8% (v/v) improved the bacteriological efficacy of formaldehyde. Under these conditions, a 1% formaldehyde solution allows eradication of all organisms tested. Similar results were observed in multiple-use dialyzers inoculated with the same organisms. There was no effect of incubation at 40 degrees C on the in vitro clearance determinations of new and reused dialyzers.

Disinfection↗
PubMed1985

Vascular access for hemodialysis. Patency rates and results of revision.

Over a 4-year interval, 324 arteriovenous conduits were created in 256 patients with end-stage renal disease as access for chronic hemodialysis. These included 154 Cimino fistulae, 163 polytetrafluoroethylene (PTFE) grafts, and seven miscellaneous grafts. Satisfactory patency rates were demonstrated for as long as 4 years for both Cimino fistulae and PTFE grafts by life-table analysis. Failures of Cimino fistulae usually occurred early in the postoperative period, secondary to attempts to use inadequate veins. Thrombosis caused the majority of PTFE graft failures and was generally the result of venous stenosis. Correction of such venous stenosis is mandatory to restore graft patency and can result in prolonged graft survival.

Adolescent↗
PubMed1984

Complement activation and hypersensitivity reactions to dialysis membranes.

Certain patients receiving hemodialysis experience recurrent chest pain, dyspnea, and hypotension during exposure to new cuprophane-membrane dialyzers (the "first-use syndrome"). Because activation of complement may be involved in these events, we examined in vivo complement activation with new cuprophane membranes and in vitro activation by zymosan in 6 such patients, and compared them with 10 patients who did not have symptoms during dialysis. All patients with the first-use syndrome had maximal complement activation 10 minutes after initiation of dialysis, with C3a des-arginine (desArg), the stable metabolite of C3 activation, equal to 8533 +/- 157 ng per milliliter (mean +/- S.E.M.). In asymptomatic patients the maximal C3a desArg value occurred at 15 minutes and was only 2907 +/- 372 ng per milliliter (P less than or equal to 0.0001). At a concentration of 3.8 x 10(-5) g of zymosan per milliliter, patients with the first-use syndrome had a C3a desArg level of 29.6 +/- 1.4 micrograms per milliliter, whereas it was only 16.6 +/- 2.3 micrograms per milliliter in asymptomatic patients (P less than or equal to 0.0001). Two other patients, who experienced cardiopulmonary collapse during the first two minutes of dialysis, had a C3a desArg level of 18,900 and 7800 ng per milliliter, respectively. We conclude that the occurrence of adverse symptoms associated with new cuprophane-membrane dialyzers correlates with complement activation.

Adult↗
PubMed1984

Hypertension and proteinuria: long-term sequelae of uninephrectomy in humans.

Renal function and blood pressure were assessed in 52 renal allograft donors 10 years or more following uninephrectomy, and their current function compared to their pre-uninephrectomy function as well as to age- and sex-matched control subjects consisting of inpatient potential renal donors and a normal "outpatient" population. The results show no significant deterioration in renal function as determined by serum creatinine or creatinine clearance, as a function of years post-uninephrectomy or age at the time of donation. A higher incidence of proteinuria and hypertension was found in male donors as compared to their pre-uninephrectomy values and to age- and sex-matched, inpatient and outpatient control subjects. Female donors had increased proteinuria when compared to pre-uninephrectomy and to age-matched, inpatient potential donors. However, the extent of proteinuria and hypertension was not significantly different from outpatient age-matched females with two kidneys. In our population, uninephrectomy is associated with mild proteinuria and hypertension.

Adult↗
PubMed1984

Biocompatibility of dialysis membranes: effects of chronic complement activation.

The ability of three dialysis membranes (cuprophane, cellulose acetate, and polymethylmethacrylate) to activate complement was studied prospectively in ten chronic dialysis patients using new and reused membranes. Patients were dialyzed for 1 month with each type of membrane. New cuprophane membranes caused the most intense activation, while polymethylmethacrylate (PMMA) surfaces caused the least degree of complement activation. Reuse decreases the capacity of the cuprophane membrane to activate complement but does not significantly alter the capacity of cellulose acetate membranes. The extent of complement activation paralleled the ability of these membranes to induce neutropenia. Recurrent dialysis with new cuprophane and cellulose acetate membranes leads to a decrease in pre-dialysis and "rebound leukocytosis" neutrophil count, as well as a more intense activation of complement and an enhanced endogenous clearance of products of complement activation. The clinical sequelae of recurrent complement activation are discussed.

Biocompatible Materials↗
PubMed1984

Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis.

Activation of complement and the relative number of C3b receptors expressed by neutrophils was assessed in patients undergoing haemodialysis with new and reused cellulosic membranes, and with polymethylmethacrylate (PMMA) membranes. Activation of complement was assessed by radioimmunoassay of plasma C3adesArg, and neutrophil C3b receptors were measured by fluorescent flow cytometry of cells indirectly stained with F(ab')2 anti-C3b receptor. During first use of cellulosic dialysis membranes by four patients, the mean expression of C3b receptors by neutrophils in blood taken from the afferent line of the extra-corporeal system after 10, 20, 60 and 120 min of dialysis increased to 127, 189, 255 and 296%, respectively. The mean plasma C3adesArg concentrations in the corresponding samples of blood were 225, 320, 236 and 160% of the pre-dialysis levels. During third and fifth use of the same membranes by these patients, the mean C3b receptor expression by neutrophils did not exceed 150% of the predialysis determination, and correspondingly minimal increases in plasma C3adesArg were observed. Analysis of blood taken simultaneously from the afferent and efferent lines of the first use cellulosic dialysis system indicated that the increase in C3b receptor expression by neutrophils and generation of C3adesArg occurred when blood came in contact with the dialysis membrane. Haemodialysis of four additional patients with the non-complement activating PMMA membrane caused only modest or no increases in neutrophil C3b receptors. Thus, complement activation in vivo is associated with up-regulation of neutrophilic C3b receptors, indicating that this cellular response previously described only in model, in vitro systems, is a physiological mechanism by which this cell can augment its capacity for responding to C3b opsonized material.

Biocompatible Materials↗
PubMed1982

Hemodialysis-associated neutropenia and hypoxemia: the effect of dialyzer membrane materials.

The fall in white blood cells (WBC) and arterial oxygen pressure that occurs during hemodialysis was investigated as a function of different dialysis membranes and different sterilization methods. 8 chronic hemodialysis patients were studied and each was dialyzed with three different membranes: cellulosic hollow fiber, polyacrylonitrile flat sheet and polymethylmethacrylate hollow fiber. Each dialyzer was studied with a dry sterilization method and after formalin treatment. Arterialized blood gas, bicarbonate and WBC were drawn at various intervals throughout dialysis. The effect of the sterilization method was minimal. Cellulosic membranes were shown to cause significantly more neutropenia (p less than 0.001) and hypoxemia (p less than 0.01) than the other two membranes. No significant differences was seen in pH, PCO2 and bicarbonate. The results indicate differences in biocompatibility between different membranes. Clinical implications are discussed.

Adult↗