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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 127 records · Page 7Linked to original sources
PubMed1991

Steady-state pharmacokinetics of hydroxychloroquine in rheumatoid arthritis patients.

Steady-state pharmacokinetics of hydroxychloroquine (HC) sulfate (Plaquenil) were studied in five volunteers with rheumatoid arthritis who had taken 6 mg/kg/d of the drug for at least six months. Blood samples were drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following an oral dose. Both whole blood and plasma were assayed by an HPLC method for HC and its metabolites desethylhydroxychloroquine, desethylchloroquine, and didesethylchloroquine. A 24-hour urine collection was obtained and assayed for the same compounds. The pharmacokinetics of HC and its metabolites conformed to the model predicted by single-dose studies. During the 24-hour period the absorption phase and both early and late distribution phases were seen. Variation in mean maximum/minimum concentration was 40 percent. Renal clearance accounted for only 16 percent of unchanged HC (22 percent of total drug and metabolites) and did not correlate with creatinine clearance.

Administration, Oral↗
PubMed1991

Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group.

On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Can screening for melanoma and skin cancer save lives?

Although screening for melanoma and skin cancer is theoretically appealing, too few data exist to evaluate its effectiveness. The rising incidence and mortality rates of melanoma and the continued incurability of metastatic disease underscore the desperate need for effective screening. The extraordinary incidence of NMSC is a public health problem, but the value of screening for NMSC has not been established. The AAD screening program offers an opportunity to obtain critical data. Further research must make our screenings more effective and efficient. We need rigorous design and evaluation of all screening efforts. In the absence of a randomized controlled trial, other design measures, with careful tracking of incidence and mortality, are critical to assessing whether screening for melanoma and skin cancer can reduce morbidity and save lives.

Humans↗
PubMed1990

Day 7 marrow response and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features.

The percent of marrow blasts on day 7 of therapy was determined for 128 children with previously untreated acute lymphoblastic leukemia and white blood count (WBC) greater than or equal to 50,000/microliters and/or lymphomatous features enrolled in the Childrens Cancer Study Group trial of the Berlin Frankfurt Munster 76/79 regimen (CCG-193P). Patients received four-drug induction therapy including vincristine, prednisone, l-asparaginase, and daunomycin. Ninety-seven patients had fewer than 25% marrow blasts on day 7. Of these, 94 survived and maintained remission through day 28 and were designated early responders. Thirty-one patients had greater than 25% marrow blasts on day 7. Of these, 28 survived and achieved remission on day 28 and were designated late responders. The outcome of patients who underwent a day 7 marrow aspiration was similar to those who did not. Early responders had a 77.4% +/- 4.5% (standard deviation) 3-year estimated disease free survival, while late responders had 47.3% +/- 9.8% (P less than 0.001). Early responders had a superior outcome both in the subset with an initial WBC less than 50,000/microliters (P = 0.025) and in the subset with a WBC greater than or equal to 50,000/microliters (P = 0.01). The day 7 marrow response had prognostic value in this population of children with unfavorable presenting features who received four-drug remission induction therapy.

Adolescent↗
PubMed1990

Alfentanil controls the haemodynamic response during rapid-sequence induction of anaesthesia.

Laryngoscopy and tracheal intubation often cause hypertension and tachycardia, which may be exaggerated during rapid-sequence induction of anaesthesia. A placebo-controlled, double-blind study was conducted in 60 patients to determine dose-response and effects on myocardial performance of alfentanil when used to attenuate this cardiovascular response. Patients were divided into four groups to receive a pre-induction bolus from a coded syringe, which contained either normal saline (PLAC), alfentanil 30 micrograms.kg-1 (ALF 30), alfentanil 45 micrograms.kg-1 (ALF 45) or alfentanil 60 micrograms.kg-1 (ALF 60). Anaesthesia was induced in rapid sequence with thiopentone 4.0 mg.kg-1 and succinylcholine 1.5 mg.kg-1, and the trachea was intubated 60 sec later. Increases in heart rate (21 +/- 10 bpm), mean arterial pressure (28 +/- 13 mmHg), and systemic vascular resistance index (1420 +/- 780 dynes.sec-1.cm-5) were observed in response to intubation with PLAC but in none of the 3 ALF groups (P less than 0.05). However, heart rate and mean arterial pressure decreased significantly in both the ALF 45 and ALF 60 groups (P less than 0.05), whereas ALF 30 resulted in no change in these variables over time. Cardiac index, stroke volume index, and ejection fraction tended to decrease in all four groups, but none of these variables was different at corresponding time when comparing the ALF groups with PLAC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery.

A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs.

Alfentanil↗
PubMed1990

Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society.

Years of potential life lost (YPLL) is an indicator of premature mortality that complements traditional incidence and mortality rates and that facilitates comparisons among different cancers. We calculated YPLL from cutaneous melanoma and 11 other cancers routinely recorded and tracked by Surveillance, Epidemiology and End Results (SEER). YPLL from cutaneous melanoma ranked eighth for persons younger than 65 years of age and fourth for those 20 to 49 years of age. An average of 17.1 YPLL per death were due to melanoma, one of the highest rates for adult-onset cancers. The results of our study, the first to apply YPLL to cutaneous melanoma, emphasize the disproportionate impact of this cancer on young and middle-aged adults and reemphasize the importance of this cancer as a public health priority.

Adult↗
PubMed1990

A randomized double-blind comparison of fentanyl- and sufentanil-oxygen anesthesia for abdominal aortic surgery.

Twenty-four patients undergoing abdominal aortic surgery for aneurysm or occlusive vascular disease entered a randomized, double-blind protocol comparing high-dose narcotic anesthesia with fentanyl (125 micrograms/kg) or sufentanil (25 micrograms/kg). All patients received perioperative beta-adrenergic blockade therapy. Hemodynamic and electrocardiographic (leads II and V5) responses to induction, intubation, skin incision, aortic cross-clamping, and declamping were studied. Sufentanil produced a transient decrease in mean arterial pressure and a significant reduction of systemic vascular resistance during induction. However, no significant hemodynamic differences were observed between the two groups during intubation, or at any other time during surgery. To maintain mean arterial pressure within 20% of the awake control value, the fentanyl group required an average infusion of 1.0 +/- 1.1 micrograms/kg/min of nitroglycerin compared with 1.7 +/- 2.8 micrograms/kg/min for the sufentanil group. Low-dose isoflurane was required in 30% of patients in the fentanyl group, compared with 41% of the sufentanil group, for control of blood pressure. The multiple-bolus technique of narcotic administration resulted in a wide but parallel range of plasma concentrations from induction to the end of surgery with both narcotics. Mean plasma fentanyl concentrations varied between 7.2 +/- 1.4 ng/mL and 26.5 +/- 7.9 ng/mL, and mean sufentanil plasma concentrations varied between 1.0 +/- 0.1 ng/mL and 10.6 +/- 7.2 ng/mL throughout surgery. Within this range of narcotic serum levels, the authors were unable to identify a specific threshold level for either narcotic above which hemodynamic responses were consistently attenuated. A low incidence (4.5%) of intraoperative myocardial ischemia was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1990

A case-control study of alcoholic beverage consumption and breast cancer.

In many studies, moderate alcohol consumption has been associated with increases in the risk of breast cancer of about 50-100%. The authors examined recent alcoholic beverage consumption in relation to the risk of breast cancer in a case-control study of women aged less than 70 years, conducted in Toronto, Ontario, Canada, from 1982 to 1986: 607 breast cancer cases identified in a cancer hospital were compared with 1,214 controls matched to the cases on neighborhood and decade of age. The subjects were interviewed at home. Confounding factors were controlled by conditional logistic regression. The relative risk estimates for women who consumed alcohol, relative to women who drank less than one alcoholic beverage (drink) per month, were close to 1.0: for women who drank at least one alcoholic beverage per day, the multivariate estimate was 0.9 (95% confidence interval 0.6-1.2). Among subgroups of women, including those at low baseline risk, there was also no association. For a subset of cases compared with hospital controls, once again there was no association. The relative risk (RR) estimate was elevated for women who drank at least one beer daily (RR = 1.7) and reduced for women who drank at least one glass of wine daily (RR = 0.7), but neither estimate was statistically significant. The results suggest that recent alcohol consumption does not influence the risk of breast cancer. Selection bias cannot be ruled out, however. In addition, because determinants of alcohol use are not well understood, control of confounding may have been incomplete in the present study and in other observational studies of alcohol and breast cancer.

Adult↗
PubMed1990

Diazepam use in relation to breast cancer: results from two case-control studies.

The relation between diazepam use and breast cancer was explored in two case-control studies. The first (1981-1987) was a hospital-based study in the United States of 3,078 cases of breast cancer, 1,259 controls with other malignancies, and 672 controls with nonmalignant conditions. The relative risk estimates for regular diazepam use (at least 4 days per week for at least 6 months) that antedated the diagnosis of breast cancer by at least 12 months were 1.0 (95% confidence interval (CI) 0.6-1.7) using the cancer controls and 0.8 (95% CI 0.4-1.8) using the noncancer controls. Risk factors for breast cancer were taken into account in the estimates. There was no association for regular use lasting at least 5 years or for regular use that took place exclusively in the recent or more distant past. The second study (1982-1986), conducted in Toronto, Ontario, Canada, was community-based, and included 607 cases of breast cancer and 1,214 neighbor controls selected from municipal voting and census records. After control of confounding, the relative risk estimate for regular diazepam use was 0.8 (95% CI 0.5-1.3). Again, there was no association for long-term, past, or recent regular use. The results of both studies suggest that regular diazepam use does not increase the risk of breast cancer. The findings are strengthened by the similarity of the results using three different control groups--women with cancer, women with nonmalignant conditions, and neighbors.

Adolescent↗
PubMed1990

The prognostic value of testicular biopsy in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

One of the objectives of Childrens Cancer Study Group (CCSG) study 141 (CCG-141) was to determine the frequency of occult testicular leukemia (TL) after 3 years of disease-free survival (DFS) and to retreat boys with occult TL to prolong their subsequent DFS. Of the 494 boys entered on study, 255 (51.6%) were in complete continuous remission (CCR) 3 years after entering remission and an additional eight were in CCR 3 years after localized extramedullary relapse and retreatment; 263 boys were eligible for testicular biopsy. Elective testicular biopsy was performed on 235 (89.4%) boys. Of the 204 (86.8%) boys with negative biopsies, 175 (85.8%) remained in CCR 10 to 12 years after diagnosis and 25 (12.3%) relapsed, 11 (44%) of whom died. Isolated overt TL occurred in four (2.0%) and all remained in CCR 22+ to 60+ months after re-treatment. Of the 26 boys with occult TL, 16 (62%) remained in CCR. Ten (38%) relapsed despite local testicular irradiation and systemic re-treatment; six of the 10 died. Of the 26 boys who did not undergo biopsy, 21 (80.8%) remained in CCR; two (7.7%) developed isolated overt TL. DFS after testicular biopsy was significantly better in boys without occult TL (P = .001). Occult TL after 3 years of CCR represents aggressive minimal-residual disease and carries a worse prognosis than absence of TL. Initial treatment should be directed at obviating occult and overt testicular relapse. Conventional therapy as used in this study was suboptimal in preventing subsequent bone marrow (BM) relapse and death. If occult TR is identified during or at the end of planned therapy, a higher salvage rate may require intensified alternate therapy. As such, testicular biopsies may be clinically useful. Further investigation is limited by the relative rarity of, and the lack of identifying features in boys with occult TL.

Antineoplastic Combined Chemotherapy Protocols↗