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Biomedical subjects

J J Crowley

Publications and source records attributed to J J Crowley.

At least 127 records · Page 7Linked to original sources
PubMed1987

Evaluation of a proposed method for phenytoin maintenance dose prediction following an intravenous loading dose.

A large clinical study, designed to investigate the induction of theophylline metabolism by phenytoin, provided the opportunity to test a previously proposed method for estimating dose requirements of phenytoin. This method involves prediction of the oral maintenance dosage from data obtained following the administration of an intravenous loading dose. In 30 subjects, trough plasma concentration at steady-state were 12.0 +/- 4.9 micrograms X ml-1 (mean +/- SD) and differed by -2.7 +/- 39.3% from a mean target plasma concentration of 12.5 +/- 1.5 micrograms X ml-1. A Bayesian regression programme was used to forecast an estimate of each subject's individual pharmacokinetics. These were then used to predict the steady-state plasma concentrations which would be expected from a standard dosing regimen (4 mg per kg per day). When compared to the results expected from the use of this standard dosage, the proposed method gave acceptable steady-state plasma phenytoin concentrations with significant reductions in deviations from target concentrations. This method for the rapid individualization of phenytoin dosage requirements provides an improvement over more traditional methods of choosing an arbitrary dose adjusted for body weight followed by dosage adjustments based on achieved plasma concentration.

Adult↗
PubMed1987

Fatal liver disease associated with alpha 1-antitrypsin deficiency PiM1/PiMduarte.

A 53-yr-old man with a rare form of partial alpha 1-antitrypsin deficiency, PiM1/PiMduarte, died of endstage cirrhosis. Typical cytoplasmic alpha 1-antitrypsin globules were present in the hepatocyte cytoplasm. Initial protease inhibitor phenotyping on the patient was reported as normal PiM1 in more than one laboratory. This case emphasizes the diagnostic importance of alpha 1-antitrypsin and illustrates the point that protease inhibitor phenotyping without family genotyping may be misleading in heterozygous patients with liver disease.

Cytoplasm↗
PubMed1987

Cigarette smoking and theophylline metabolism: effects of phenytoin.

The induction of theophylline clearance by phenytoin was investigated in 12 young male subjects (six nonsmokers and six cigarette smokers). Each subject received intravenous theophylline to determine baseline pharmacokinetics. This was followed by an intravenous loading dose of phenytoin sodium and oral maintenance dosing for 2 weeks, after which the intravenous theophylline study was repeated. Phenytoin concentrations were similar in nonsmokers (10.8 +/- 2.0 micrograms/ml) and smokers (11.5 +/- 0.9 micrograms/ml). Control theophylline elimination half-life was 35% less and clearance 88% greater in smokers than in nonsmokers. The proportionate changes in half-life (26.8% +/- 5.6% in smokers and 25.8% +/- 3.5% in nonsmokers) and clearance (48.0% +/- 10.1% in smokers and 39.7% +/- 7.2% in nonsmokers) as the result of phenytoin induction were similar in both groups. These results demonstrate that the induction of theophylline clearance by phenytoin is additive to that caused by cigarette smoking and provide support for the suggestion that theophylline metabolism is influenced by multiple polymorphisms.

Adult↗
PubMed1987

Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.

In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Cellular sources of thymidine nucleotides: studies for PET.

The relative utilization of endogenously synthesized thymidine nucleotides and exogenously supplied thymidine analog was compared in a number of mammalian cell lines, tissues, and tumors. To measure the relative utilization, cells were incubated in tissue culture media containing the thymidine analog [3H]-5-bromo-2'-deoxyuridine (BUDR). After extraction of the DNA, the degree of substitution of the thymidine by BUDR was determined by density gradient centrifugation. All the cell lines and tissues tested utilized both exogenous BUDR and endogenous thymidine sources to a similar extent. The relative utilization of the exogenous pathway could be manipulated by varying the exogenous concentration of BUDR. Our results demonstrate that one can predict the relative utilization of these two pathways and can calculate the effective specific activity of the intracellular thymidine nucleotide pool. Such information is needed in interpreting 11C-labeled thymidine uptake as measured by positron emission tomography.

Animals↗
PubMed1986

Therapeutic concentrations of theophylline and enprofylline potentiate catecholamine effects and inhibit leukocyte activation.

Methylxanthines are primary agents used in treatment of hypersensitivity disease. Because polymorphonuclear leukocyte (PMN) activation is associated with generation of potent inflammatory mediators, xanthine effects on the PMN respiratory burst were studied. Enprofylline, a xanthine with important therapeutic potential, does not antagonize adenosine and was contrasted with theophylline. Although enprofylline was more potent at low concentrations, both drugs exhibited dose-dependent inhibition of PMN activation at concentrations greater than 10 mumol/L (1.8 micrograms/ml). Oxygen metabolite generation was decreased by 30% to 40% at therapeutic drug concentrations and by 85% at 1 mmol/L of theophylline. Inhibition by isoproterenol or prostaglandin E2 but not dibutyryl cAMP was potentiated by either xanthine. Isoproterenol effects were also increased when isoproterenol was evaluated in whole blood specimens obtained from subjects after a loading dose of aminophylline. Although these results were most compatible with cAMP phosphodiesterase inhibition, other commonly proposed mechanisms of methylxanthine activity were also studied. Theophylline but not enprofylline blocked adenosine inhibition of PMN activation. Neither xanthine shifted the calcium dose-response when PMNs were activated with calcium ionophore. Because oxygen metabolites generated by the FMN are mediators of inflammation and hypersensitivity, direct inhibition of PMN activation as well as potentiation of catecholamine activity may be important therapeutic effects of theophylline and enprofylline.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Theophylline clearance in patients with severe chronic obstructive pulmonary disease receiving supplemental oxygen and the effect of acute hypoxemia.

The effect of hypoxemia on the disposition of theophylline was examined in 10 stable patients with chronic obstructive pulmonary disease (COPD) receiving chronic theophylline and supplemental home oxygen therapy. Pharmacokinetics after intravenous theophylline were estimated on the second day of supplemental oxygen (PaO2, 69 +/- 4 mmHg; mean +/- SEM) and on the second day of room air breathing (PaO2, 43 +/- 3) using a randomized cross-over design. On each occasion stable isotope-enriched theophylline (10 mg, m/z 183) was administered intravenously along with the regular oral dose of theophylline (m/z 180). Concentrations of both forms of theophylline in plasma samples obtained over 24 h were measured using mass spectrometry. Theophylline clearance during oxygen therapy (0.048 +/- 0.005 L/h/kg) was similar to that during room air breathing (0.050 +/- 0.004 L/h/kg). Values for elimination half-life (7.6 +/- 0.8 versus 6.8 +/- 0.6 h) and volume of distribution at steady state (0.450 +/- 0.021 versus 0.429 +/- 0.024 L/kg) were also unchanged. The volume of distribution of theophylline was inversely related to arterial pH during oxygen therapy (pH range, 7.32 to 7.44) and during room air breathing (pH range, 7.33 to 7.47). Although hypoxemia does not alter theophylline clearance in patients with COPD, theophylline loading doses may need adjustment according to arterial pH because of an effect on volume of distribution.

Administration, Oral↗
PubMed1985

Correlation of serum cyclosporine concentration with renal dysfunction in marrow transplant recipients.

We retrospectively analyzed the relationship of serum cyclosporine concentration to renal dysfunction in 63 marrow transplant recipients who received cyclosporine for prophylaxis of acute graft-versus-host disease. Patients were divided into three groups according to their mean trough cyclosporine concentration for the first 28 days of therapy: less than 150, 150-250, and greater than 250 ng/ml. Baseline renal function and exposure to nephrotoxic antibiotics was comparable in the three groups. Renal dysfunction was defined as doubling of baseline serum creatinine. The likelihood of developing renal dysfunction was analyzed with Kaplan-Meier product limit estimates. The log-rank test was used to compare the three groups. Fifty-four (86%) of the patients developed renal dysfunction. The incidence of renal dysfunction was 73%, 95%, and 100%, and it developed at a median of 46, 29, and 20 days in patients with a mean trough concentration of less than 150, 150-250, and greater than 250 ng/ml, respectively (P less than 0.001). Eight of the nine patients who did not develop renal dysfunction had a mean trough concentration of less than 150 ng/ml. These data indicate that the incidence and the rate of development of renal dysfunction are related to serum cyclosporine concentration.

Adolescent↗
PubMed1984

Recurrent infection with herpes simplex virus after marrow transplantation: role of the specific immune response and acyclovir treatment.

Herpes simplex virus (HSV) reactivation is common after marrow transplantation, with some patients developing frequent and severe recurrences. Sixty patients were studied to determine both the effect of the specific lymphocyte response to HSV on subsequent recurrences and the effect of acyclovir treatment on restoration of this response. Patients with a positive response after the first HSV recurrence had fewer second recurrences (13 of 28 vs. 18 of 19; P less than .01) and at a longer interval when they did recur (42 vs. 27 days; P less than .0001). Conversely, patients treated with acyclovir had more frequent second recurrences than did those not treated (18 of 21 vs. 13 of 26; P less than .05) and they were at a shorter interval when they did recur (27 vs. 36 days; P = .001). Treated patients also had lower specific lymphocyte responses to HSV. These data confirm the importance of the specific immune response to HSV in the determination of the course of HSV infection after marrow transplant.

Acyclovir↗
PubMed1984

Prognostic value of blood glucose in Hodgkin's disease.

Subjects with Hodgkin's disease and an initial blood glucose greater than 115 mg/dL had an impressively shorter survival than those with a glucose below that level. The same is true if the groups are formed from those having glucose above or below 100. The correlation between glucose and survival persisted after allowing for the survival effects of histology, stage, symptom class, and age.

Age Factors↗
PubMed1983

Acute renal toxicity with combined use of amphotericin B and cyclosporine after marrow transplantation.

The role of cyclosporine alone or in combination with amphotericin B in the development of renal toxicity was evaluated in 47 marrow transplant recipients. Cyclosporine alone was given to 21 patients and 10 received cyclosporine plus amphotericin B. These were compared with 16 patients who received methotrexate and amphotericin B. Serum creatinine doubled within 14-30 days in 8 of 21 patients who received only cyclosporine. Of 16 patients given amphotericin B in conjunction with methotrexate, only 3 doubled their serum creatinine within 5 days of starting amphotericin B. In contrast, of 10 patients who received amphotericin B in combination with cyclosporine, 5 doubled and 3 tripled their serum creatinine within 5 days. This increase in creatinine was significantly greater than that seen in patients receiving cyclosporine alone or methotrexate and amphotericin B combined. These results suggest that administration of cyclosporine and amphotericin B simultaneously should be undertaken with caution to avoid severe renal toxicity.

Adolescent↗
PubMed1982

Prognostic value of serum lactic dehydrogenase level in Hodgkin's disease.

The serum LDH level determined at time of diagnosis provides important prognostic information about patients with Hodgkin's disease. The median survival of patients with a normal value was 129 months, whereas those with elevated values had a median survival of only 39 months. The prognostic power of LDH persisted after adjustment for age, symptom class, stage, or histology. When the Cox proportional hazards regression method was used to simultaneously adjust for age, histology, symptom class, and stage, elevated enzyme levels still were correlated with short survival. (J Lab Clin Med 99:382, 1982.)

Female↗
PubMed1981

Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer.

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.

Adult↗
PubMed1981

Vindesine. A phase II trial in advanced breast cancer patients.

A phase II trial of vindesine (VDS), a new vinca alkaloid, has been carried out in 40 patients with metastatic breast cancer. Patients entered in the study had been previously treated with an average of two chemotherapy regimens. Treatment was given as a weekly I.V. bolus of VDS at 3 mg/m2. The response rate in 31 evaluable patients was 19%, i.e., one complete response (CR), four partial responses, and one improvement in osseous disease (IMP). In 36 patients evaluable for toxicity, neurological and hematological toxicity was most significant. Half the patients treated had received previous vincristine therapy; this factor did not appear significant with regard to toxicity or response to VDS.

Adult↗
PubMed1979

Prognostic signs in chronic myelocytic leukemia.

In a retrospective search for prognostic factors in 127 patients with chronic myelocytic leukemia we found that thrombocytopenic patients had a significantly shortened life-span. Patients with the Philadelphia chromosome lived longer and were significantly younger than those lacking it. Females lived longer than males. Numerous other single features failed to correlate significantly with survival, but several combinations of two did. Patients having a low hematocrit with a low white blood count had an impressively short life-span compared to all others. Those having a high cholesterol and a low uric acid survived significantly longer than all others.

Blood Cell Count↗