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Biomedical subjects

R Hakim

Publications and source records attributed to R Hakim.

At least 37 records · Page 2Linked to original sources

Use of Medicare data to identify incident breast cancer cases.

Surveillance, Epidemiology and End Results (SEER) data from the National Cancer Institute (NCI) provide reliable information about cancer incidence. However, because SEER data are geographically limited and have a 2-year time lag, we evaluated whether Medicare data could provide timely information on cancer incidence. Comparing Medicare women hospitalized for breast cancer with women reported to SEER, Medicare data had high specificity (96.6 percent), yet low sensitivity (59.4 percent). We conclude that Medicare hospitalization data can identify incident cases for cancers that usually require inpatient hospitalization. For cancers that often only receive outpatient treatment, such as breast cancer, additional Medicare data, such as physician bills, are needed to understand the entirety of treatment practices.

Aged↗

Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease.

Intravenous immune globulin (IVIg) has been advocated as efficacious therapy for a variety of disorders including idiopathic thrombocytopenic purpura and Kawasaki disease. Several reports have also documented the effectiveness of IVIg in systemic lupus erythematosus (SLE). Two patients with symptomatic SLE and ESRD were treated with IVIg. Both patients tolerated IVIg administration well and demonstrated clinical and serologic improvement. Both individuals also experienced a transient decline in serum albumin concentration with IVIg treatment. The mechanisms by which IVIg might have effected improvement in these patients are varied and are likely related to the immunomodulatory actions of IVIg. The reversible change in albumin concentration seen in these individuals may be secondary to abrupt alterations in oncotic homeostasis. Despite this unusual effect, the documented improvement in these patients suggests that IVIg therapy may be of benefit in patients with active SLE and ESRD. Further studies are warranted to examine the mechanisms by which IVIg may exert its therapeutic effect.

Adult↗

Hemodialysis membrane biocompatibility in acute renal failure.

Hemodialysis is a lifesaving procedure for patients with acute renal failure. Nevertheless, the institution of hemodialysis may result in a continued or accelerated decline in renal function. Loss of osmotic drive and hypotension may be partially responsible for this observation. However, multiple lines of evidence suggest that the nature of the hemodialysis membrane also influences renal function following acute renal failure. The cellulosic hemodialysis membrane activates humoral pathways and the cellular elements of blood. The inflammatory responses entrained from the activation result in hypersensitivity reactions attributable to anaphylatoxin generation, hypoxemia, increased susceptibility to infection, and catabolic events. In addition, recent studies indicate that the use of bioincompatible membranes delays recovery from acute renal failure. Increased numbers of neutrophils are found in the glomeruli following exposure to cellulosic membranes, suggesting that inflammatory events induced by complement activation may mediate continuing renal injury and prolonged recovery from acute renal failure. Membrane choice for patients with acute renal failure is emerging as an important therapeutic consideration, just as it is for those patients on long-term dialysis.

Acute Kidney Injury↗

The use of the Codman-Medos Programmable Hakim valve in the management of patients with hydrocephalus: illustrative cases.

Cerebrospinal fluid shunting is an important method of treating hydrocephalus. It sometimes has been difficult to achieve the optimum CSF pressure and ventricular size after shunt placement. Hydraulic and mechanical mismatching may occur, creating either overdrainage, as manifested by slit ventricle syndrome and/or subdural hygromas; or underdrainage, as manifested by a failure of the ventricles to change in size, with persistence of symptoms. A variable pressure valve (Codman-Medos Programmable Hakim valve system) has been developed to allow non-invasive increase or decrease in cerebrospinal fluid pressure in differentials of 10 mm of water within a range of 30-200 mm of water. This allows the neurosurgeon to adjust the pressure to the patient's particular clinical needs at any given moment. As part of a pilot study of the valve's safety, 13 patients in this center were treated with this programmable shunting system from October 1991 to January 1993. Twelve patients were over age 18 and one was younger than this. Six patients had previously been shunted with other valve systems, and the remaining seven had never been shunted before. The etiology of hydrocephalus included idiopathic normal pressure hydrocephalus (6 patients), aqueductal stenosis (3 patients), Chiari malformation (2 patients), meningitis (1 patient), and unknown etiology (1 patient). This paper describes the use of this valve in five illustrative cases; slit ventricle syndrome in an adult, chronic ventriculomegaly with aqueductal stenosis (2 cases), and idiopathic normal pressure hydrocephalus (2 cases). This programmable valve has been particularly useful in gradually decreasing ventricle size in idiopathic normal pressure hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bradykinin generation by dialysis membranes: possible role in anaphylactic reaction.

Several recent reports have described a high incidence of anaphylactic reactions in patients being dialyzed with high-flux membranes while simultaneously using angiotensin-converting enzyme inhibitors. Many of these reports implicate polyacrylonitrile (PAN) as the membrane commonly involved in these reactions. To elucidate potential mechanisms of these anaphylactic reactions, whether dialysis membranes can activate the Hageman factor-dependent (contact) pathways as assessed by the in vitro generation of activated Hageman factor (Hfa), as well as the formation of kallikrein and subsequent bradykinin generation was examined. Both cuprophane (CUP) and PAN membranes were able to activate Hageman factor and convert prekallikrein to kallikrein as measured by an ELISA against kallikrein-C1-inactivator complexes. Subsequently, the active kallikrein was able to cleave bradykinin from its endogenous substrate, high-molecular-weight kininogen. However, it was found that the PAN membrane consistently led to an earlier and significantly higher formation of Hfa and kallikrein when compared with CUP. Importantly, there was also a pronounced but transient generation of bradykinin by the PAN membrane, in contrast to slower bradykinin formation by CUP, with both normal and uremic blood. It was proposed that the early and vigorous bradykinin generation induced by the contact of blood with PAN could explain, in part, the pathogenesis of the reported anaphylactoid reactions.

Acrylic Resins↗

Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells.

We have developed a bioartificial liver support system utilizing hollow-fiber bioreactor, plasmapheresis and microcarrier cell culture technologies. Liver cells were obtained through portal vein perfusion with ethylenediaminetetraacetate or ethylenediaminetetraacetate/collagenase. A mathematical model of mass transport in a hollow-fiber module, at various plasma flow velocities and system configurations, was developed. The bioartificial liver's ability to carry out specific differentiated metabolic liver functions was tested in vitro and in vivo. A reproducible large-animal model of acute ischemic liver failure was developed. Most major first-generation cyclosporine and 19-norterstosterone metabolites were isolated after substrate addition to the bioartificial liver in vitro. After bioartificial liver treatment for 6 hr (with dog or pig liver cells), dogs with acute liver failure had significantly lower serum ammonia and lactate levels and significantly higher serum glucose levels than did control animals treated with a bioartificial liver system inoculated with microcarriers alone. In addition, bioartificial liver-treated animals had significantly higher mean systolic blood pressures than did controls. Liver cell viability at the end of the 6-hr in vivo experiment was greater than 90%.

Animals↗

Use of a novel bioartificial liver in a patient with acute liver insufficiency.

We have developed a bioartificial liver support system (BAL) using porcine hepatocytes attached to microcarriers and placed on the outer surface of hollow fibers. The BAL system was attached to a plasmapheresis device that was then used to treat the plasma of a patient with acute liver failure. Our aim was to test the efficacy and safety of this system after a single short treatment period. A patient with alcohol-induced, severe, acute liver failure manifested by coagulopathy, rising plasma ammonia level, and deteriorating mental status was studied. The procedure was well tolerated by the patient, who remained hemodynamically stable throughout the treatment period. A marked increase in coagulation factor V, VII, VIII, and IX activities, a decrease in serum ammonia level (120 to 32 mumol/L), a twofold increase in all serum amino acids except for aminobutyric acid, and an improvement in mental status were noted after a 6-hour treatment period. This preliminary report of the first use of this novel BAL system in conjunction with plasmapheresis appears promising. A clinical study is now in progress to prove its efficacy.

Adult↗

Modulation of granulocyte LAM-1 and MAC-1 during dialysis--a prospective, randomized controlled trial.

Hemodialysis with first-use cellulosic dialysis membranes results in activation of the alternative pathway of complement and profound neutropenia followed by rebound leukocytosis. The neutropenia has been shown to be associated with increased expression of adhesion receptors and pulmonary sequestration of granulocytes. However, the mechanism underlying the return of the granulocytes has not been elucidated. We determined simultaneously the changes in the granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor during dialysis using a complement activating and a non-complement activating membrane, in a randomized, cross-over study. With initiation of dialysis with cellulosic membranes, there was a rapid and prominent increase in the expression of MAC-1 receptors. At the nadir of granulocyte count, 15 minutes after initiation of dialysis with the complement activating membrane, there was a four-fold increase in the MAC-1 receptor expression. At the same time, there was a two-fold decrease in LAM-1 expression. There were no changes in the expression of two other granulocyte receptors CD11a and CD15 which are known not to be modulated during granulocyte activation. Granulocytes harvested during dialysis and which had high MAC-1 and low LAM-1 expression had a significantly decreased adherence to endothelial cell monolayers. Dialysis of the same patients with non-complement activating membranes resulted in no significant change in the expression of these receptors on granulocytes nor in their adherence to endothelial cells. These results shed new light on the mechanism of the cyclical granulocytopenia and rebound granulocytosis during dialysis with new cellulosic membranes.

Cell Adhesion↗

The dose of hemodialysis according to dialysis prescription in Europe and the United States.

Prior research has shown that, controlling for age and diabetes, patients with end-stage renal disease in Europe generally have better rates of survival than do ESRD patients in the U.S. This analysis compares the dose of hemodialysis prescription in the two regions. Based on the European Dialysis and Transplant Association Registry (EDTA), the U.S. Renal Data System (USRDS), and other sources, European and U.S. ESRD patients were compared by demographic and anthropometric characteristics, dialyzer characteristics, and duration of dialysis treatment times. Average body weight and body mass indices were found to be similar for the ESRD populations of the two societies, suggesting the same overall requirements for dialysis therapy. During 1986 to 1988, dialyzers selected in Europe had a larger surface area by at least 20 percent compared to those selected in the U.S. In addition, duration of hemodialysis treatment times were on average 23.5% longer for EDTA patients. Dialyzer blood flows were not available for EDTA patients, but if EDTA blood flows resemble U.S. practices, total urea clearance per week was at least 29% higher in Europe than in the U.S. Combining similar patient characteristics with substantially greater total urea clearance per week, the hemodialysis prescription in Europe was substantially higher than in the U.S. for the time period of this study.

Europe↗

Reactive oxygen species production by monocytes and polymorphonuclear leukocytes during dialysis.

Intradialytic production of reactive oxygen species (ROS) by monocytes and polymorphonuclear leukocytes (PMNL) was examined separately in six hemodialysis patients. Samples obtained 15 minutes after initiation of dialysis with new cuprophane membranes demonstrated significantly increased (P less than 0.05) ROS production in both cell populations as measured by the fluorescence of a specific intracellular marker (2',7'-dichlorofluorescein diacetate [DCFH-DA]) assayed by flow cytometry. Granulocytes harvested during dialysis also showed decreased responsiveness to exogenous C5a and F-Met-Leu-Phe (FMLP) at 15, 30, and 60 minutes after initiation of dialysis (P less than 0.05). Our data suggest that hemodialysis with cuprophane membrane is associated with monocyte and PMNL activation as shown by production of ROS coincident with peak activation of the complement cascade; these granulocytes become refractory to further stimulation with C5a and FMLP during dialysis.

Adult↗

Complement activation retards resolution of acute ischemic renal failure in the rat.

We investigated the role of complement activation on the resolution of acute ischemic renal failure in the rat. Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with acute renal failure were exposed to daily zymosan infusion (an activator of the complement system), or to blood incubated with cuprophane (CUP) or polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour proteinuria on Day 3 and Day 5 following ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically. Zymosan and cuprophane exposed rats had a significant delay in the recovery of renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of zymosan-exposed rats to infusion of deferoxamine (DFO), a potent inhibitor of hydroxyl radical formation (OH.). Infusion of DFO prior to zymosan significantly improved recovery of renal function. We also measured urinary thromboxane B2 levels in these groups of rats. While the groups of rats exposed to zymosan had the highest levels of thromboxane B2, these levels were not different between the groups exposed to zymosan alone, or to zymosan and DFO. These observations suggest a role for hydroxyl radicals in the prolongation of renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with acute renal failure.

Acute Kidney Injury↗

Phagocytosis in uremic and hemodialysis patients: a prospective and cross sectional study.

Leukocyte response to phagocytic challenge was assessed in uremic and hemodialysis patients in a prospective and cross sectional study. Using latex, zymosan and staphylococcus as phagocytic challenge, the utilization of glucose-I-C14 and the generation of reactive oxygen species was measured in these patients. In uremic, non-dialysis dependent patients, the response to phagocytosis was significantly reduced when creatinine exceeded 6 mg/dl and prior to initiation of dialysis (mean serum creatinine 9.3 +/- 0.3 mg/dl) was less than half that of patients with normal renal function (P less than 0.01). In a prospective study of 15 patients initiated on dialysis, the metabolic response of their leukocytes was assessed sequentially. In eight patients, initiation of dialysis with cuprophane (Cu) membrane lead to a further decline (60%) in their metabolic response to phagocytosis at the end of four weeks of dialysis compared to pre-initiation of dialysis (P less than 0.01), whereas in seven other patients, dialysis with non-complement activating membranes did not result in a significant decline. Prospective cross-over studies of chronic hemodialysis patients corroborated these findings; eight patients dialyzed with new CU membranes had a significant decline of their metabolic response to phagocytic challenge acutely at the end of each dialysis and in pre-dialysis samples after two weeks of Cu dialysis, whereas their response returned back to baseline after two weeks of dialysis with non-complement activating membrane. In prospective and cross sectional studies, a decreased response to phagocytic stimulus was a predictor of hospitalization, primarily for infectious reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗

Effects of recombinant human growth hormone in adults receiving maintenance hemodialysis.

Administration of recombinant human growth hormone stimulates protein synthesis, decreases urea generation, and improves nitrogen balance in individuals with normal renal function. However, little information is available concerning the effects of growth hormone in patients with renal disease. This pilot study evaluated urea kinetics and clinical/metabolic responses to short-term growth hormone administration in five clinically stable adult patients requiring maintenance hemodialysis for end-stage renal failure. The dialysis prescription, medications, and oral calorie and protein intake of each patient remained constant during an initial control week and a subsequent 2-wk growth hormone treatment period. During treatment, growth hormone (5 or 10 mg) was administered s.c. immediately after each dialysis session. Protein and calorie intake, vital signs, body weight, and other clinical parameters remained stable throughout the 3-wk study. BUN values fell significantly (approximately 20 to 25%) during growth hormone administration compared with control week values. Similarly, urea kinetic modeling demonstrated a significant reduction in urea generation and the protein catabolic rate during each week of growth hormone treatment. Plasma insulin-like growth factor I levels rose significantly, and serum phosphorus and intact parathyroid hormone levels fell significantly during growth hormone administration. Serum glucose and other blood values remained stable. This preliminary study suggests that growth hormone administration reduces urea generation and improves the efficiency of dietary protein utilization in stable adult hemodialysis patients. Growth hormone may be a useful adjunctive therapy to diminish body protein catabolism in this patient population.

Adult↗

[Follow-up of patients suspected of glaucoma using computer-assisted analysis of the optic disk].

The Optic Nerve Head Analyzer was used for longitudinal monitoring of glaucoma suspects. Forty-one patients (76 eyes) were monitored for more than 12 months and 29 patients (51 eyes) for more than 18 months. A significant (p less than or equal to 0.06) decrease in the neuroretinal rim area was found in 8 of 51 eyes monitored greater than 18 months. Thirty-eight of 19 healthy subjects served as the control group. Only 1 of these 38 healthy eyes showed a significant decrease in the neuroretinal rim area (p = 0.04); this decrease is perhaps an artifact caused by the limited accuracy of the Optic Nerve Head Analyzer. From our data we conclude that longitudinal monitoring of patients for glaucoma by means of the Optic Nerve Head Analyzer is an adequate method of detecting ongoing glaucoma damage.

Adolescent↗