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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 163 records · Page 9Linked to original sources

Modified BFM therapy for children with previously untreated acute lymphoblastic leukemia and unfavorable prognostic features. Report of Children's Cancer Study Group Study CCG-193P.

The Children's Cancer Study Group's (CCG) clinical trials in acute lymphoblastic leukemia (ALL) prior to 1981 consistently demonstrated that patients presenting with a white blood cell count (WBC) greater than or equal to 50,000/microliter or the "lymphoma syndrome" had a less than 40% 3-year event-free survival (EFS). The Berlin Frankfurt Munster (BFM) 76/79 study suggested that the prognosis of these patients could be improved. Before testing this therapy in a randomized setting, 29 CCG institutions used it for treatment of 209 newly diagnosed children with ALL and an initial WBC greater than or equal to 50,000/microliter or the lymphoma syndrome. In the intensive phases of therapy, 77% of cumulative parenteral doses and 55% of cumulative oral doses were within 10% of protocol requirements or were modified appropriately for reported toxicity. One hundred ninety-five patients achieved remission (93.3%). Eleven patients died in remission (5.6%)--10 during the intensive reinduction/reconsolidation phase. The 4-year EFS (+/- 1 SD) was 62% (+/- 3.7%) with a median follow-up of 40 months. Only one patient has had an isolated CNS relapse. These results appear superior to past CCG studies for high-risk patients and extend observations made from studies of similar therapy.

Adolescent↗

Postoperative hypertension: a comparison of diltiazem, nifedipine, and nitroprusside.

In previous studies, the treatment of postoperative hypertension with sodium nitroprusside induced ischemic metabolism without a decrease in coronary sinus blood flow. In contrast, the calcium antagonists diltiazem and nifedipine reduce blood pressure and may improve myocardial metabolism. A prospective randomized trial was performed in 62 patients, in whom hypertension developed (mean arterial pressure greater than 95 mm Hg) after coronary bypass procedures, to compare diltiazem (n = 22), nifedipine (n = 20), and nitroprusside (n = 20). All three agents reduced blood pressure equally (p less than 0.0001, by analysis of variance). Heart rate decreased with diltiazem (p = 0.006) but increased with nifedipine and nitroprusside (p less than 0.05). Left ventricular diastolic function (the relation between left atrial pressure and left ventricular end-diastolic volume) was not changed with the three drugs. Systolic function (the relation between systolic blood pressure and left ventricular end-systolic volume) was depressed with diltiazem (p = 0.05 by analysis of covariance) and nifedipine (p = 0.05) but not with nitroprusside. Myocardial performance (the relation between left ventricular stroke work index and end-diastolic volume) was depressed most by diltiazem (p = 0.001 by analysis of covariance), and to a lesser extent with nifedipine (p = 0.03), but not with nitroprusside. Myocardial lactate flux in response to the stress of atrial pacing decreased with nitroprusside but not with diltiazem or nifedipine (p = 0.03 by analysis of variance). Diltiazem and nifedipine are effective agents for treating postoperative hypertension after coronary artery bypass operations.

Clinical Trials as Topic↗

The measurement of performance in childhood cancer patients.

The performance status of the child with cancer is an important outcome consideration in pediatric oncology research and practice. However, no single measure for children has been available. This is a report of the development and standardization of such a scale. The play-performance scale for children is a parent-rated instrument which records usual play activity as the index of performance. Performance status ratings were obtained on three groups of children: patients (n = 98), patients' siblings (n = 29), and an independent sample of hospital employees' children (n = 40). Children with all types and stages of childhood malignant neoplasms were represented. Test results established the parent as a competent, reliable rater and demonstrated the validity of the scale. Interrater reliability was examined using correlational statistics and percentage agreement. Agreement between parents was good, and there were no systematic rater biases. In addition, parents' ratings significantly discriminated differences in levels of functioning (mean score, patients 75.4 versus siblings 97.4). Correlational and analysis of variance (ANOVA) procedures demonstrated that the play-performance scale was significantly related to the global performance measures of experienced clinicians and was sensitive to change. Inpatients received a mean score of 42.3, outpatients 90.7, and normals 98.2. These findings indicate that the scale is both feasible and effective. It is concise, can be administered repeatedly even to extremely ill patients, and uses parents as observer reporters. The play-performance scale for children provides quantifiable, reproducible, and meaningful data, which is necessary for effective monitoring and management of the child with cancer.

Activities of Daily Living↗

Terminal differentiation-resistant epidermal cells in mice undergoing two-stage carcinogenesis.

We have used an in vivo-in vitro approach to investigate the cellular aspects of two-stage skin carcinogenesis. Female SENCAR mice initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were promoted twice weekly with 12-O-tetradecanoylphorbol-13-acetate (TPA). Epidermal cultures from untreated or TPA-treated mice had few focus-forming cells resistant to calcium-induced terminal differentiation. Cultures from mice treated with MNNG alone formed numerous foci. Brief promotion (four TPA treatments) of MNNG-treated mice produced fewer but statistically larger foci, suggesting that TPA was selecting against more slowly growing cells. MNNG plus TPA-treated mice with very early papillomas produced more and larger foci than those due to MNNG treatment alone, suggesting that the papillomas may have comprised calcium-resistant cells. These cells may indeed be initiated cells since a permanent cell line arising after MNNG plus brief TPA treatment eventually formed histological papillomas in vivo. If calcium-resistant cells are initiated, then there were many more initiated cells in the skin (with or without TPA treatment) than papillomas expected, implying that either some initiated cells never formed papillomas, or that a significant accumulation of initiated cells had already occurred in the skin within 2 weeks of MNNG treatment. Subsequent TPA promotion of these cells apparently produced a toxic response that passively selected for more rapidly growing initiated cells, which eventually accumulated into papillomas.

Animals↗

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis.

Plasma levels of hydroxychloroquine (HCQ) and its metabolites were measured, by high performance liquid chromatography, in 37 rheumatoid arthritis patients who could be clearly distinguished as responders (n = 28) or nonresponders (n = 9) to HCQ, 400 mg/day. Efficacy in both groups was determined by the patients' erythrocyte sedimentation rates, joint counts, morning stiffness, global assessments, concurrent drug therapies, and grip strength. The response rate was 76%. Responders had a mean HCQ level of 213 ng/ml, versus 306 in nonresponders (P less than 0.05). The mean level of HCQ plus total metabolites in responders was 363 ng/ml, versus 554 in nonresponders (P less than 0.01). We conclude that monitoring plasma HCQ levels is unlikely to be helpful in individualizing effective drug dosage.

Arthritis, Rheumatoid↗

Acquired subglottic cysts in premature infants.

Advances in the management of premature infants have resulted in improved survival. However, long-term intubation may produce associated laryngeal complications. We report 12 infants and children who developed subglottic cysts following long-term intubation as newborns. The majority of the cysts were in the posterior subglottic larynx. Laser excision of the cysts was undertaken in 8 patients and 3 underwent removal with cupped forceps. Recurrent cysts in 3 patients required more than one endoscopic procedure. The differential diagnosis of stridor in infants who have required long-term intubation includes subglottic cysts. The cysts are not always obvious at endoscopy and indeed may be buried below the mucosa within a soft tissue subglottic stenosis. Their presence may be suspected when tiny beads of mucus are released when laser surgery of a soft tissue stenosis is applied. Successful management of these cysts includes early precise diagnosis, with careful identification of these cysts to differentiate them from other types of subglottic stenosis. An initial attempt of conservative management with endoscopic excision is made. If this fails, an anterior cricoid split may be indicated in cases where the cysts are associated with soft tissue subglottic stenosis. Tracheostomy may be unavoidable in some cases.

Cysts↗

Failure of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to inhibit cell-cell coupling in newborn mouse epidermal cells and Chinese hamster V79 cells under non-standard culture conditions.

The function of the skin tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) during two-stage carcinogenesis in mice remains obscure because of TPA's numerous phenotypic effects. In vitro studies under established conditions have generated substantial interest in TPA's ability to inhibit, although transiently in some cases, direct cell-cell coupling in several permanent cell lines, by analogy allowing latent 'initiated cells' to escape homeostatic controls in vivo. Using different culture conditions designed to improve the growth of newborn mouse epidermal cells, we examined dye coupling in these cells, and metabolic co-operation in V79 cells, finding no effect of TPA on coupling. It appears that this effect of TPA is overly sensitive to in vitro conditions. Since a corresponding physiological effect has not yet been demonstrated in vivo, future studies should be directed to establish that coupling inhibition by TPA actually does occur and plays some role during tumor promotion in vivo, and is not merely a characteristic of certain culture systems.

Animals↗

Epithelial ovarian cancer and coffee drinking.

A recent report from a case-control study in Greece suggested that coffee consumption is related to an increase in the risk of ovarian cancer. This hypothesis was examined in a hospital-based case-control study in the US. Information on coffee drinking and other factors was obtained from 290 incident cases of epithelial ovarian cancer and compared with that of 580 controls with non-malignant conditions of acute onset and 476 controls with cancer of other sites. Adjustment was made for the potential confounding effects of several factors, including the major known risk factors for ovarian cancer. The estimated relative risk for drinking five or more cups of coffee per day, relative to none, was 1.1 (95% confidence interval, 0.6-2.0) using the controls with non-malignant conditions and 1.0 (0.5-1.8) using the controls with cancer. The estimates for drinking less than five cups per day were greater than 1.0, but this could have been due to chance. The consumption of decaffeinated coffee and tea also appeared to have no influence on risk. The evidence from this study suggests that, if coffee drinking increases the risk of ovarian cancer, the effect is small.

Adult↗

Improved survival of infants less than 1 year of age with acute lymphoblastic leukemia treated with intensive multiagent chemotherapy.

Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Early disease recurrence, rather than excessive toxicity and complications resulting in limitation of therapy is the major factor responsible for this disappointing outcome. The CCG-192P trial was a groupwide pilot study of the Childrens Cancer Study Group for the treatment of ALL in patients at high risk for relapse, which was defined by wbc count greater than 50 X 10(3)/microliters at diagnosis. Because of the recognized poor prognosis, all infants less than 1 year of age were entered in this study regardless of wbc count at diagnosis. Therapy included intensive induction and consolidation followed by a cyclic, sequential maintenance program. The CNS prophylaxis consisted of intrathecal chemotherapy and cranial irradiation, which was deferred until patients were greater than 1 year of age. During the period January 1982 to January 1984, 27 infants ranging in age from 2 days to 11 months who had ALL were entered in this study; 71% had wbc counts greater than 50 X 10(3)/microliters, and 23% presented with CNS leukemia. Complete remission was achieved in 93% of the patients. The median duration of remission is 17 months. With a median follow-up of 43 months, the life-table estimate of event-free survival (EFS) is 36% at 4 years. A recently reported historical control group of infants with ALL who were treated with previous Childrens Cancer Study Group protocols demonstrated a median remission duration of 8 months and an estimated EFS of only 21% at 4 years. Toxicity and therapy-related complications were not observed more frequently in infants than in older patients treated with this protocol. However, EFS of infants was significantly worse than that of patients greater than 1 year of age (P = less than 0.001). All four CNS relapses occurred in patients who had received cranial irradiation. A wbc count less than 50 X 10(3)/microliters at diagnosis demonstrated significance (P = 0.03) as a favorable prognostic indicator in this small patient sample. Although these data are preliminary, they suggest that intensive therapy is reasonably well tolerated by infants and results in prolongation of remission duration and improved EFS.

Age Factors↗

Management of fibromyalgia, a distinct rheumatologic syndrome.

The pathophysiology and management of fibromyalgia, a unique nonarticular rheumatologic syndrome characterized by diffuse musculoskeletal aches and pains, stiffness, discrete tender points at typical soft-tissue sites, and a characteristic sleep disturbance, are reviewed. The prevalence and incidence of fibromyalgia are not known, but it is one of the most common conditions seen by rheumatologists (after degenerative joint disease and rheumatoid arthritis). It was previously thought to involve inflammation of fibrous intermuscular septa and is sometimes referred to in the literature as fibrositis. It is not primarily psychogenic, but psychological factors may contribute. The tender points are the key to diagnosis. Fibromyalgia may be classed as primary (when no underlying disease is present) or secondary (when an associated condition exists). The pathophysiology of fibromyalgia is unknown but appears to involve complex interactions of central neurotransmitters with a relationship to pain perception, mood, and sleep. Treatment is empiric; nondrug treatment involving education, relaxation, and increased physical activity is essential. Few controlled trials of drug therapy have been conducted. Analgesics, anti-inflammatory drugs, phenothiazines, tricyclic antidepressants, and the tricyclic muscle relaxant cyclobenzaprine have been used; low doses of amitriptyline or cyclobenzaprine provide increased control of pain and mood.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Risk factors for breast cancer in black women.

Risk factors for breast cancer were examined in black women in a hospital-based case-control study of 529 black women with breast cancer and 589 controls. Late age at menarche was associated with a reduced risk of breast cancer. Women having 5 or more children had a reduced risk relative to that of women with fewer or no children. Late age at first birth was associated with an elevated risk of breast cancer. Among postmenopausal black women, obesity [as measured by body mass index (BMI)] was associated with an increased risk; among premenopausal women, there was no association of breast cancer with BMI. Women whose menopause occurred at or after age 50 were at increased risk relative to those whose menopause occurred earlier. There was no association between number of years of education and breast cancer in black women. History of benign breast disease and history of breast cancer in mother or sisters both were risk factors. The risk factor profile for breast cancer in black women was similar to that observed in whites.

Adult↗

Hb Bicêtre or alpha 2 beta(2)63(E7)His----Pro in a white male: clinical observations over a period of 25 years.

A description is given of clinical observations over a period of 25 years for a 26-year-old white male with a heterozygosity for the beta-chain variant, Hb Bicêtre, in which beta 63His is replaced by Pro. The variant was identified through analysis of tryptic peptides from a digest of the beta X-chain isolated by PCMB precipitation and purified by chromatography. Similarity between the clinical histories of the first (French) heterozygote and our patient was most striking, including improvement after splenectomy.

Adult↗

Bulk characterization and scanning electron microscopy of hydrogels of P(VA-co-NVP).

The bulk properties of uncrosslinked and crosslinked random copolymers of vinyl alcohol and N-vinyl-2-pyrrolidone [P(VA-co-NVP)] are reported. Analytical studies were performed by infrared and nuclear magnetic resonance spectroscopy, gel permeation chromatography, potentiometric titration, elemental analysis and scanning electron microscopy. The microscopic studies elucidated the effect of freeze-drying on the network surface topology. The results indicate macrosyneresis of the copolymer hydrogels upon freeze-drying even at -23 degrees C. Rapid collapse of the hydrogel structure is seen upon removal of the bulk and interfacial water in the frozen state.

Biocompatible Materials↗