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Biomedical subjects

R A O'Reilly

Publications and source records attributed to R A O'Reilly.

At least 19 recordsLinked to original sources
PubMed1999

Splenomegaly at a university hospital compared to a nearby county hospital in 317 patients.

Splenomegaly and massive splenomegaly were diagnostically evaluated retrospectively at Stanford University Hospital in 147 patients over 8 years and compared to the nearby county hospital (Santa Clara Valley Medical Center; VMC) in 170 inpatients over 11 years. Hematologic diseases at Stanford (data for VMC in parentheses) occurred in 66% (35%; p < 0.001) of the patients with splenomegaly and in 84% (54%; p < 0.001) of those with massive splenomegaly. Hepatic diseases occurred in 9% (36%; p < 0.001) of the patients with splenomegaly and in 5% (29%; p < 0.001) of those with massive splenomegaly. Splenectomy was performed in 71% of the patients at Stanford and in 9% of those at VMC (p < 0.001). The combined Stanford-VMC series showed significant associations (p < 0.01): for hematologic diseases with massive splenomegaly, lymphadenopathy, and blood cytoses; for hepatic diseases with hepatomegaly, cytopenias as hypersplenism, and abnormal liver function tests, and for infectious diseases with fever.

Adolescent↗
PubMed1998

Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing warfarin therapy unchanged.

STUDY OBJECTIVES: To study the efficacy and safety of partially correcting therapeutic anticoagulation by administering oral vitamin K1. DESIGN: Prospective interventional trial. SETTING: Outpatient anticoagulation clinic. PATIENTS: Patients who required reversal of their normal or excessive therapy with oral anticoagulant drugs were recruited. INTERVENTIONS: All patients received a single oral dose of vitamin K1. The dose was calculated using a regression formula and was intended to decrease the international normalized ratio (INR) to a predetermined value. Patient follow-up continued for 8 weeks. We compared the actual change of the INR to the predicted change. RESULTS: Sixty-five reversals of anticoagulant therapy were initiated in the study group. Sixty-four of the 65 reversals were successful. The mean (+/-SEM) initial INR was 2.6+/-0.1 for the preprocedure patients and 8.4+/-0.5 for the excessively anticoagulated patients. The predicted change in the INR correlated with the actual change (r = 0.92, p < 0.0001). There were no thromboembolic events and only one hemorrhagic complication. The mean (+/-SEM) dose of oral vitamin K1 was 5.0+/-0.3 mg for the preprocedure patients and 10.0+/-1.0 mg for the excessively anticoagulated patients. CONCLUSIONS: The administration of a single oral dose of vitamin K1 is a safe and effective method for partially reversing anticoagulant therapy without disrupting the daily maintenance dose of warfarin. A reliable regression formula was developed to predict the dose of vitamin K1 needed to achieve the desired INR.

Anticoagulants↗
PubMed1998

Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients.

Splenomegaly was studied retrospectively at the University of California, San Francisco, School of Medicine, on all patients (N = 2,056) for the years 1913 to 1962. The patients were classified into several diagnostic groups, and these groups were tested for statistical significance (chi(2)) with many clinical and laboratory variables to determine their predictive value. Hematologic disorders were associated with 57% of cases of splenomegaly and 81% of cases of massive splenomegaly. Among patients with splenomegaly, 19% had infectious diseases, 11% had hepatic diseases, and 9% had congestive or inflammatory disorders. The residual 4% were considered to have primary splenic disorders or a disorder of unknown cause. The commonest diseases associated with splenomegaly were hematologic (acute and chronic leukemias), infectious (malaria, endocarditis, and tuberculosis), hepatic (chronic liver disease), congestive (congestive heart failure), inflammatory (thyrotoxicosis), and other (cancers not metastatic to the spleen). The diseases most frequently associated with massive splenomegaly were the chronic leukemias. The disease with the highest incidence of massive splenomegaly was myelofibrosis (23 of 29 patients, 78%). Splenectomy was performed in 154 patients (7%), primarily for hematologic amelioration and hepatic hypersplenism. Hematologic diseases showed significant associations with lymphadenopathy, generalized lymphadenopathy, massive splenomegaly, and cytoses (P .001) and with progressive splenic enlargement (P < .02). Infectious diseases showed significant association with fever, and hepatic diseases showed significant association with abnormal results of liver function tests (P < .001). The findings of this retrospective study should be validated prospectively.

Adolescent↗
PubMed1998

Splenomegaly in 2,505 patients at a large university medical center from 1913 to 1995. 1963 to 1995: 449 patients.

Splenomegaly was studied retrospectively at the University of California, San Francisco (UCSF), School of Medicine in 301 patients from 1963 to 1995 and compared with the UCSF service of the San Francisco General Hospital Medical Center (SFGH) in 148 patients from 1979 to 1994. The combined 449 patients were classified into several diagnostic groups and were studied by means of several clinical and laboratory associations. Hepatic disease in the percentage of patients at UCSF (with those at SFGH given in parentheses) was associated with splenomegaly in 29% (41%), hematologic disease, 32% (16%); infectious diseases, 16% (36%); congestive or inflammatory disease, 10% (4%); primary splenic disease, 6% (1%); other, 5% (1%); and cause unknown, 2% (1%). Massive splenomegaly occurred in 27% of the patients of the combined series, particularly in patients with hematologic diseases. The acquired immunodeficiency syndrome (AIDS) occurred in more than half of the patients with infectious diseases at SFGH and was four times frequent than in the patients at UCSF. The commonest diseases associated with splenomegaly were hematologic (lymphoma), hepatic (chronic liver disease), infectious diseases (AIDS and endocarditis), congestive (congestive heart failure), primary splenic (splenic vein thrombosis), and other (malignancy not metastatic to the spleen). In 11 patients with AIDS and massive splenomegaly, Mycobacterium avium complex occurred in 8 (73%). Splenectomy was performed in 117 patients (26%), primarily for hematologic amelioration. I conclude that for splenomegaly of unknown origin, the invasive procedure of choice for patients with hematologic associations may be a bone marrow biopsy; for hepatic association, a liver biopsy; and for infectious disease associations, a lymph node biopsy, before any consideration of a diagnostic splenectomy.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Splenomegaly at a United States County Hospital: diagnostic evaluation of 170 patients.

Splenomegaly was studied at a municipal teaching hospital in an 11-year retrospective review. The 170 patients were classified into six diagnostic groups. The associated clinical and laboratory features were tested for statistical association (X2), to determine predictive values. Hepatic diseases caused 36% of the splenomegaly; hematologic, 35%; infectious diseases (ID), 16%; inflammatory, 5%; primary splenic, 4%; and other, 3%. The acquired immunodeficiency syndrome (AIDS) occurred in 54% of patients with ID. Hematologic diseases were significantly associated (P < 0.01) with massive splenomegaly, left upper quadrant (LUQ) abdominal tenderness, and all blood "cytoses." The most common disease with massive splenomegaly was myelofibrosis. Surprisingly, hepatic diseases caused 29% of massive splenomegaly. Hepatic diseases were significantly associated (P < 0.01) with hepatomegaly, abnormal liver-function tests (LFT), and blood "cytopenias." Compared with previous reports, both congestive heart failure and endocarditis now rarely cause splenomegaly. All blood "cytopenias" had highly significant associations (P < 0.01) only with hepatic diseases, which suggests that hypersplenism remains a useful concept for the splenomegaly of liver disease.

Adolescent↗
PubMed1992

The mechanism of the interaction between amiodarone and warfarin in humans.

Amiodarone decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Warfarin excretion products were quantified and clearance and formation clearance values calculated. Amiodarone and metabolites inhibited the reduction of (R)-warfarin to (R,S)-warfarin alcohol-1 and the oxidation of both (R)- and (S)-warfarin to phenolic metabolites. Inhibition of warfarin hydroxylation by amiodarone in human liver microsomes was compared with the in vivo results. In agreement, the in vitro data indicates that amiodarone is a general inhibitor of the cytochrome P450 catalyzed oxidation of both enantiomers of warfarin, but the metabolism of (S)-warfarin is more strongly inhibited than that of (R)-warfarin. These data suggest that the enhanced anticoagulant effect observed when amiodarone and warfarin are coadministered is attributable to inhibition of P4502C9, the isozyme of P-450 primarily responsible for the conversion of (S)-warfarin to its major metabolite, (S)-7-hydroxywarfarin.

Adult↗
PubMed1992

Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects.

Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S)-warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible for termination of the anticoagulant effect, was most strongly inhibited. Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation. The enhanced anticoagulant effect observed when miconazole and warfarin are coadministered may result from inhibition of P4502C9, the isozyme of P450 primarily responsible for the conversion of (S)-warfarin to (S)-7-hydroxy-warfarin. Because miconazole inhibits a number of P450 isozymes, in addition to P4502C9, it can be expected to lead to interactions with other drugs whose primary metabolism is controlled by these enzymes.

Adult↗
PubMed1987

Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans.

To evaluate a stereoselective interaction for amiodarone and racemic warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral amiodarone, 400 mg daily, for the hypoprothrombinemic duration. Both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01) were significantly increased. The experiments were repeated separately with the R- and S-warfarin enantiomorphs. S-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01). R-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.001). Thus amiodarone augmented the anticoagulant effect nonstereoselectively by reduced metabolic clearance of both warfarin enantiomorphs. Amiodarone and racemic warfarin can be a dangerous combination, particularly when either drug is added to a stabilized regimen of the other drug, unless the prothrombin times are monitored carefully.

Adult↗
PubMed1987

The effect of sulfinpyrazone on the disposition of pseudoracemic phenprocoumon in humans.

The effect of sulfinpyrazone on the pharmacokinetics and disposition of the enantiomers of pseudoracemic phenprocoumon was assessed by analyzing serial plasma, urine, and fecal samples for parent drug and metabolites by GC/MS. Essentially all of the administered dose could be accounted for either as parent drug, known metabolites, or their conjugates. Phenprocoumon and the 7-hydroxymetabolite represented the major materials recovered. All drug-related materials excreted into the urine were extensively conjugated. Sulfinpyrazone treatment did not affect the hypoprothrombinemia produced by phenprocoumon nor did it significantly alter the plasma elimination kinetics of the individual (R)- and (S)-enantiomers. However, an apparent increased free fraction of both enantiomers in plasma and inhibition of 7-hydroxylation of (S)-phenprocoumon were observed in the presence of sulfinpyrazone. The results of this study are contrasted with those of a previous study on the interaction between sulfinpyrazone and the structurally similar coumarin anticoagulant warfarin.

4-Hydroxycoumarins↗
PubMed1987

The mechanism of the warfarin-rifampin drug interaction in humans.

The mechanism of the drug interaction in humans between warfarin and rifampin was investigated by monitoring the elimination kinetics and metabolic disposition of a single oral dose of pseudoracemic warfarin by GC/MS. The decrease in hypoprothrombinemia observed with concomitant administration of therapeutic doses of rifampin was accompanied by a substantial decrease in the elimination half-lives of both warfarin enantiomers. Rifampin increased the clearance of (R)-warfarin threefold and the clearance of (S)-warfarin twofold. The excretion profiles for warfarin and its metabolites in urine and feces were similar for both control and treated subjects with the exception that 4'-hydroxywarfarin (stereoselective for the (S)-enantiomer) was observed when rifampin was administered. 4'-Hydroxywarfarin is a metabolite of the drug hitherto undetected in vivo in humans. Based on formation clearance values estimated for 6-, 7-, and 8-hydroxywarfarin, rifampin appears to increase the clearance of the parent drug by induction of the cytochrome P-450 isozyme(s) responsible for aromatic hydroxylation.

Adult↗
PubMed1986

The warfarin-sulfinpyrazone interaction: stereochemical considerations.

To allow the simultaneous evaluation of the interaction between sulfinpyrazone and each enantiomer of racemic warfarin, pseudoracemic warfarin (1:1 12C-R(+) and 13C-S(-)warfarin) was given to six normal subjects both before and during oral sulfinpyrazone dosing. Serial blood and urine samples were analyzed for unchanged warfarin and its metabolic products by GC/MS. A mass balance of an oral dose of pseudoracemic warfarin, containing a tracer quantity of 14C-warfarin, was carried out in one of the subjects by monitoring 14C levels in urine and feces for 15 days. Concomitant sulfinpyrazone dosing markedly increased hypoprothrombinemia, decreased clearance of (S)-warfarin, and increased clearance of (R)-warfarin. Sulfinpyrazone also decreased the urinary excretion of warfarin-related products but increased their fecal excretion by an equivalent amount. Virtually all of the administered warfarin dose could be accounted for either as unchanged drug or known metabolites. Pharmacokinetic analysis of the data suggests the following: At least four distinct enzymes (two oxidases and two reductases) are involved in the metabolism of warfarin. Sulfinpyrazone increases the hypoprothrombinemia caused by warfarin primarily by inhibition of the cytochrome P-450-mediated oxidation of (S)-warfarin, the biologically more potent enantiomer. The increased clearance of (R)-warfarin results not from induction, but from its selective displacement from plasma protein binding sites.

Administration, Oral↗
PubMed1985

Metabolic fate of phenprocoumon in humans.

Samples of urine and feces were collected daily from a normal human volunteer who had received a dose of pseudoracemic phenprocoumon [an equimolar mixture of (R)-[12C]- and (S)-[2-13C]phenprocoumon] containing a tracer dose of 10 microCi of [14C]phenprocoumon and analyzed by TLC, HPLC, and GC-MS. After 25 days, 96% of the radiolabeled material was recovered (62.8% in urine and 33.3% in feces). By isotopic dilution and comparison to the Rf values, retention times, and mass fragmentograms of synthetic standards, the metabolites of the drug were identified as the 4'-, 6-, and 7-hydroxy analogues of phenprocoumon. Virtually all of the recovered radioactivity could be accounted for by the parent drug (approximately 40%) and the three metabolites (approximately 60%). The formation of both 4'-(8.1% of administered dose) and 7- (33.4% of administered dose) hydroxyphenprocoumon was highly stereoselective, giving S/R ratios of 2.86 and 1.69, respectively. The formation of 6- (15.5% of administered dose) hydroxyphenprocoumon showed little stereoselectivity (S/R ratio equal to 0.85). The urinary excretion pattern was also confirmed in four additional healthy male subjects who received a single oral dose of pseudoracemic phenprocoumon and whose urine was analyzed by GC-MS. All the drug-related materials (both hydroxylated metabolites and parent compound) that were excreted into the urine were extensively conjugated.

4-Hydroxycoumarins↗
PubMed1985

Delayed hemolytic transfusion reaction associated with Rh antibody anti-f: first reported case.

A delayed hemolytic transfusion reaction (DHTR) occurring in a 30-year-old Caucasian man is described. His blood groups were B, CDe/cDE (R1R2, f-) K-, S-s+, Fy (a + b-), and Jk (a + b +). Eight days after receiving two units of packed red blood cells, his urine was strongly positive for hemoglobin; serum-free hemoglobin was 125 mg/dl. Serum contained a clearly reactive Rh antibody of anti-f specificity and a weakly reactive anti-Kell. The DHTR was probably caused by an anti-f alloantibody appearing as an anamnestic response to transfusion of seemingly compatible, but f-positive blood.

Adult↗
PubMed1985

Hemoglobin E and pregnancy.

Hemoglobin E occurs in 30 million people, primarily Southeast Asians. Their resettlement within the US has dramatically increased the incidence of E hemoglobinopathies. A gravid Vietnamese woman with thalassemia major is reported herein. Her pregnancy was complicated by severe anemia, intrauterine growth retardation, and a paraspinal mass representing extramedullary hematopoiesis. The diagnosis of hemoglobin E/beta o-thalassemia was established when analysis of her hemoglobin showed 60% F, 40% E, and 0% A. The patient was transfused with packed red blood cells to maintain the maternal hematocrit at 30%. A term growth-retarded infant was delivered who had severe thrombocytopenia and an imperforate anus. The infant's thrombocytopenia responded only to infusion of maternal platelets. The differential diagnosis and expected hematologic manifestations of the various E hemoglobinopathies are detailed. Hematologic and obstetric guidelines for management during pregnancy are offered.

Adult↗
PubMed1984

Comparative interaction of cimetidine and ranitidine with racemic warfarin in man.

Cimetidine potentiates the anticoagulant effect of warfarin sodium, but in one small study ranitidine hydrochloride did not. Furthermore, these drugs have not been compared in the same subjects. Eleven normal subjects received single oral doses of 1.5 mg/kg racemic warfarin sodium alone, with cimetidine (1,200 mg/day orally), or with ranitidine (300 mg/day orally), beginning three days before the warfarin and daily thereafter for the duration of hypoprothrombinemia. Blood samples were obtained daily for determination of prothrombin times and warfarin concentrations. Cimetidine augmented both the hypoprothrombinemia and the blood concentrations of warfarin, but ranitidine did not. Substituted imidazoles like cimetidine inhibit hepatic microsomal activity, which may cause reduced metabolic clearance of warfarin and augment its anticoagulant effect. Ranitidine, lacking these effects, may be safer for patients undergoing anticoagulation who require H2-receptor antagonists.

Adult↗