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Biomedical subjects

J Fareed

Publications and source records attributed to J Fareed.

At least 361 records · Page 20Linked to original sources
PubMed1980

Lithium carbonate therapy for cluster headache. Changes in number of platelets, and serotonin and histamine levels.

Three groups of patients were studied: Group A consisted of 12 patients with cluster headache that was treated with lithium carbonate. Group B consisted of six patients with cluster headache that was managed with other drugs. Group C consisted of five patients with muscle contraction headache who received lithium. Serum lithium levels, platelet count, platelet serotonin levels, and platelet-rich plasma histamine levels were determined before and during therapy. The frequency of the headache and levels of serotonin and histamine tended to follow a parallel course in groups A and B: as the headache frequency dropped, serotonin and histamine levels fell. The stable period was characterized by little change in serotonin and histamine levels. Recurrences of headaches were accompanied by a return of serotonin and histamine to pretreatment levels. The course of cluster headache is related to changes in serotonin and histamine levels. Lithium, by modifying the headache course, changes serotonin and histamine levels.

Adult↗
PubMed1980

New perspectives in coagulation testing.

The field of coagulation testing has undergone some major technological and conceptual developments, which are briefly reviewed here. The assessment of coagulation parameters is no longer restricted to the study of clot formation and its dissolution. The understanding of the biochemical nature of coagulation processes, coupled with the development of new therapeutic agents in the treatment of hemostatic disorders, has brought about the development of fast, reliable, and clearly defined laboratory test procedures to evaluate the components of this system. The introduction of methods involving synthetic substrates has been very significant because many of the coagulation parameters can now be measured with a spectrophotometer or fluorometer, by methods that lend themselves to the automation found in most large clinical chemistry laboratories. In our laboratory, we use automated synthetic-substrate methods for antithrombin-III, plasminogen, and prothrombin, and are developing the synthetic-substrate assay equivalent of clot-based prothrombin time and partial thromboplastin. Immunological methods such as laser/rate nephelometry, enzyme-linked immunoassays, electroimmunodiffusion, and radioimmunoassays have been utilized to evaluate coagulation proteins. The relation of functional and immunological properties of these proteins to their physiological function is being studied. In coming years the testing of coagulation function will undergo some major changes and will require input from clinical chemists and other laboratory scientists to facilitate the technology transfer and proper standardization of new methods.

Antithrombin III↗
PubMed1979

Glucocorticoid and antibiotic effects on hepatic microcirculation and associated host responses in lethal gram-negative bacteremia.

Liver changes and associated host responses were evaluated in four groups of male rats, weighing 300 +/- 20 gm., which received intravenous injection of 2.2 times 10(9) live Escherichia coli. This bolus was given either without additional treatment (group A) or prior to the following regimens: intramuscular injection of gentamicin sulfate, 5 mg. per kg. (group B); intravenous injection of methylprednisolone sodium succinate, 40 mg. per kg. (group C); and intramuscular injection of gentamicin immediately after methylprednisolone sodium succinate treatment (group D). Rats given injections of saline or methylprednisolone sodium succinate served as controls. Survival rates at 10 and 20 hours were 25 per cent and 4 per cent for group A; 44 per cent and 28 per cent for group B; 94 per cent and 70 per cent for group C; 98 per cent and 98 per cent for group D, respectively. In rats of groups A and B, killed at 1, 2, 4, and 6 hours, progressive liver changes included intravascular sequestration of rapidly degranulating leukocytes, fibrinous deposits, and platelet aggregates in sinusoids as well as in spaces of Disse adjacent to subendothelial collagen, and extensive Kupffer cell disruption in association with severe midzonal necrosis. These alterations were accompanied by progressive hypoglycemia and elevations of serum enzymes, glutamic pyruvic transaminase, lactate dehydrogenase, and glutamic oxaloacetic transaminase. Hematologic studies revealed that E. coli bacteremia results in rapid leukopenia and disseminated intravascular coagulation primarily due to activation of the intrinsic coagulation pathway. All above reactions were delayed and markedly reduced in rats treated with methylprednisolone sodium succinate. The results indicate that antibiotic treatment of lethal, Gram-negative bacteremia is effective only in conjunction with early steroid treatment. The protective effects of glucocorticoids on the liver microcirculation and polymorphonuclear leukocytes appear to play a basic role in preventing the early development of disseminated intravascular coagulation, hepatocellular necrosis, and associated major host responses, thereby attenuating lethality of gram-negative septic shock.

Animals↗
PubMed1979

Inhibition of the contractile action of bradykinin on isolated smooth muscle preparations by derivatives of low molecular weight peptides.

The carbonyl terminal tripeptide sequence of bradykinin (Pro-Phe-Arg) is molecularly manipulated to obtain agents with potent antagonistic activity towards the smooth muscle contractile activity of bradykinin. Screening of various peptide derivatives revealed that heptyl amides or esters of H-D-Pro-Phe-Arg, and H-D-Phe-Phe-Arg possessed relatively stronger antibradykinin activity on the isolated smooth muscle preparation. The parent tripeptides, H-D-Pro-Phe-Arg-OH, and H-D-Phe-Phe-Arg-OH, and their amino acid components, i.e. D-Proline, D-Phenylalanine, L-Phenylalanine and Arginine, did not possess any antibradykinin activity in concentrations of up to 10(-4) M. When the heptyl derivatives of these peptides were incubated with either heparinized or citrated whole blood or plasma, the antibradykinin activity was not lost. Incubation of these peptide derivatives with either carboxypeptidase A or B did not result in any loss of the pharmacological effect. However, pancreatic protease extract produced a significant loss of the anti-oxytocic action on the isolated rat uterus preparation. H-D-Pro-Phe-Arg-NH-lauryl derivative also blocked the action of bradykinin and this effect sustained for a longer period of time comparative to the blockade with H-D-Pro-Phe-Arg-NH-heptyl derivative. In concentrations of 10(-7) M and 10(-8) M and 1 min incubation, which blocked the contractile action of bradykinin (1 nmole) on the isolated guinea pig ileum, these peptide derivatives did not block the action of acetylcholine, histamine, and serotonin. However, in concentrations of about 10(-6) M and higher with 5 min. incubation histamin is also blocked. On the isolated rat uterus preparation the contractile action of acetylcholine, angiotensin, oxytocin and vasopressin was blocked at concentrations of 10(-6) M. These findings warrant a differential pharmacological evaluation and in vivo testing of these peptide derivatives to investigate their therapeutic potential.

Acetylcholine↗
PubMed1978

A primate model for prolonged endotoxin shock. Blood-vascular reactions and effects of glucocorticoid treatment.

A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.

Animals↗
PubMedDate not supplied

Oral and subcutaneous administration of the glycosaminoglycan C3 attenuates Abeta(25-35)-induced abnormal tau protein immunoreactivity in rat brain.

High molecular weight glycosaminoglycans (GAG) and proteoglycans (PG) affect pathological changes of the brain in Alzheimer's disease (AD). PG stimulate the processing and aggregation of amyloid-beta (Abeta), protect the protein from proteolysis, and increase the formation of neurofibrillary tangles by inducing the hyperphosphorylation of tau protein. These effects may be competitively inhibited by GAG. We have studied the effects of orally (by gavage) and subcutaneously (s.c.) administered low molecular weight heparin, C3 (4-10 oligosaccharides; MW = 2.1 kDa; USP value = 12 U/mg), on abnormal tau-2 protein immunoreactivity in the rat hippocampus following a single, unilateral intra-amygdaloid administration of Abeta(25-35). Oral administration of C3 (25 mg/kg; once daily) was initiated 3 days prior to Abeta(25-35) administration, and was continued daily for an additional 14 days. S.c. administration of C3 (2.5 mg/kg, twice daily), was started 3 days prior to, and was continued for 32 days after, Abeta(25-35) administration. Animal brains were subsequently processed for tau-2, ChAT-immunoreactivity, choline acetyltransferase (ChAT) activity and acetylcholinesterase (AChE) activity. Both oral and s.c. administration of C3 attenuated Abeta(25-35) induced appearance of tau-2-immunoreactive (IR) perikarya in the ipsilateral hippocampus (P < 0.05). Hippocampal cholinergic enzyme activity in C3 treated animals was not significantly different from control animals. The present findings suggest that C3 might be used successfully to prevent abnormal tau protein formation in chronic neurologic diseases, such as AD. Moreover, our data demonstrate that the mechanism of this effect does not appear to influence the cholinergic system of the brain.

Acetylcholinesterase↗
PubMedDate not supplied

Effects of nonionic contrast media (CM) on the components of coagulation and complement systems.

Several nonionic experimental contrast media (CM) were evaluated for their effects on coagulation cascade, platelet aggregation, and the activation of complement pathways. In an in vitro system, most of the contrast media tested showed a mild anticoagulant property by prolonging the clotting times, such as partial thromboplastin time and the thrombin time of pooled normal human plasma. However, aggregation of normal human platelets by adenosine-diphosphate (ADP), collagen, epinephrine, ristocetin, and thrombin was not blocked when the platelet-rich plasma was incubated with these agents. No quantitative or qualitative changes in the complement components C3 or C4 were detected when a mixture of CM and pooled normal human serum was analyzed by radial immunodiffusion, immuno- or crossed-immunoelectrophoresis techniques. These results indicate that nonionic contrast media produce certain transient hematologic changes and should be further tested for their immunologic properties in order to establish their absolute safety in diagnostic procedures.

Blood Coagulation↗
PubMedDate not supplied

Successful use of recombinant hirudin and its monitoring by ecarin clotting time in patients with heparin-induced thrombocytopenia undergoing off-pump coronary artery revascularization.

Refludan (lepirudin-rDNA for injection) is the first direct thrombin inhibitor approved by the United States FDA for anticoagulation to patients with heparin-induced thrombocytopenia (HIT). It was monitored by ecarin clotting time (ECT) assay in patients with HIT. Case histories and clotting parameters for three patients undergoing off-pump coronary artery revascularization procedure are discussed. The first patient received r-hirudin at a dose of 0.2 mg/kg intravenous (IV) bolus followed by 0.15 mg/kg/hour infusion. The second patient received 0.4 mg/kg IV bolus followed by infusion of 0.15 mg/kg/hour infusion. The third patient with renal failure received 0.2 mg/kg IV bolus followed by an infusion of 0.02 mg/kg/hour. Blood samples were drawn at baseline, 5 minutes post bolus and every 15 minutes during the coronary artery revascularization procedure. ECT was performed immediately on the citrated whole blood samples using the ECT cards in conjunction with the point-of-care, the thrombolytic assessment system (TAS) Analyzer (Pharmanetics, Raleigh, NC). The plasma samples were then analyzed for APTT and liquid ECT assay performed on a kinetic centrifugal analyzer (ACL 300 Plus). The ECT by cards was ideally maintained above 600 seconds during the surgical procedure. Additional boluses of Refludan were given as and when necessary (ECT < 600 sec) in order to maintain adequate anticoagulation. The calculated circulating concentrations of Refludan, following a bolus administration, based on the ECT cards, liquid ECT and APTT were 3.20 +/- 1.3, 3.51 +/- 1.35 and 2.02 +/- 1.19 microg/mL, respectively.

Aged↗
PubMedDate not supplied

Low molecular weight heparins. An objective overview.

The introduction of low molecular weight heparins has added a new dimension to the management of thrombotic disorders. Ten LMWHs are currently available for clinical use. Although these agents have been primarily developed and used in European countries, other countries, including the US, have started to evaluate their usefulness. Well designed clinical trials have been carried out for different clinical indications with several of these products. In contrast to other prophylactic antithrombotic drugs (heparin, warfarin, aspirin), LMWHs have provided consistently impressive clinical results. Moreover, the other products have less desirable tolerability profiles than that of LMWHs. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of each LMWH is distinct in itself being characteristic to only that particular drug. Besides the currently available LMWH preparations, some 14 other agents are under development at this time. Although both the original and newer products have similar basic characteristics, the physicochemical properties and the pharmacological actions of each of these agents may differ significantly. All manufacturers should follow the Food and Drug Administration (FDA) guidelines and conduct their own clinical trials on each of their products. Many significant developments of LMWHs will take place in the coming years; in addition to development for prophylactic use, LMWHs will be developed for therapeutic intervention.

Heparin, Low-Molecular-Weight↗
PubMedDate not supplied

Pre- vs postoperative pharmacologic inhibition of platelets: effect on intimal hyperplasia in canine autogenous vein grafts.

Several clinical studies have shown that pharmacologic inhibition of platelets can increase the patency of vascular grafts, but only if platelet-inhibition is initiated before surgery. This study was performed to compare the efficacy of pre- vs postoperative platelet-inhibition on the development of intimal hyperplasia in canine autogenous vein grafts. Reversed femoral veins were used to bypass the ligated femoral arteries in 15 dogs. End-to-side anastomoses were constructed. Eleven dogs were treated with aspirin (325 mg QD) and dipyridamole (25 mg BID). In six dogs treatment was begun 48 hours preoperatively and continued for 3 months. In five other dogs treatment was begun 48 hours after surgery and was continued for 3 months. In 4 control dogs no antiplatelet treatment was given. Excision of the vein grafts 3 months after surgery disclosed reduced intimal hyperplasia (p < 0.05) in the grafts excised from all of the treated animals as compared with those obtained from the control animals. However, there was no difference in intimal hyperplasia observed in the dogs treated both pre- and postoperatively (11 grafts) as compared with those treated only postoperatively (9 grafts). These data demonstrate that it is not necessary to begin antiplatelet therapy preoperatively in order to inhibit intimal hyperplasia. They also suggest that preoperative antiplatelet therapy may improve early graft patency by directly preventing thrombosis, not by inhibiting the development of intimal hyperplasia.

Analysis of Variance↗
PubMedDate not supplied

Antiplatelet action of intravascular contrast media. Implications in diagnostic procedures.

The antiplatelet action of intravascular contrast media (CM) Renografin-76 (diatrizoate meglumine and diatrizoate sodium) was studied in vitro and in 21 patients undergoing radiodiagnostic procedures. In vitro studies suggested that in Renografin-76, meglumine was the chief constituent responsible for its antiplatelet action. In post-CM plasma from patients, clotting times were prolonged and platelet aggregation greatly impaired, albeit normal aggregation restored within 3 hours. Although changes in global clotting times and platelet aggregation were mostly transient, it is possible that CM usage in patients with thrombocytopenia, sickle cell phenomenon, and on anticoagulant-antiplatelet drugs may present a serious risk to their hemostatic integrity.

Adult↗
PubMedDate not supplied

A reduction in accelerated graft coronary disease and an improvement in cardiac allograft survival using low molecular weight heparin in combination with cyclosporine.

Heparin compounds are a complex mixture of mucopolysaccharides that, in addition to their anticoagulant properties, have immunosuppressive activities and affect the reparative aspects of the response to arterial injury. Heparin inhibits smooth muscle cell migration and proliferation and can alter the accumulation of the components of the extracellular matrix after arterial injury. Heparin also interacts specifically with the endothelium. Our hypothesis was that if heparin compounds do affect the immune system, coagulation, smooth muscle cell proliferation, and the endothelium, then heparin combined with cyclosporine should improve allograft survival, reduce rejection, and prevent accelerated graft coronary disease. Low molecular-weight heparins are derived from the larger molecular-weight unfractionated heparin. We chose to use low molecular-weight heparins because of their longer half-life, better bioavailability, and decreased incidence of induced thrombocytopenia and bleeding. With a rat intraabdominal heterotopic model of heart transplantation (Lewis-Brown Norway to Lewis), low molecular-weight heparin in combination with a low dose of cyclosporine (0.5 mg/kg/day) significantly improved allograft survival compared to controls and either low molecular-weight heparin or cyclosporine alone. Histologically, smooth muscle cells are an important cellular component of the lesions of accelerated graft coronary disease. In comparison to animals treated with cyclosporine alone (2 mg/kg/day), the addition of low molecular-weight heparin to cyclosporine (2 mg/kg/day) reduced the frequency and the severity of accelerated graft coronary disease and the extent of parenchymal rejection.

Abdomen↗