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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 307 records · Page 17Linked to original sources
PubMed1978

Serum inhibitors to granulopoiesis in thalassemia major.

Peripheral blood (pb) and bone marrow CFU-C were evaluated in patients with thalassemia major. A decrease in both pb and marrow CFU-C was noted when compared to normal donors and individuals with hemolytic anemia requiring transfusion therapy. Experiments suggested that a nondialyzable serum factor was resonsible for the depressed pb CFU-C in 6 and of 6 children with thalassemia. Serum lipoprotein electrophoresis revealed type IV pattern in 9 out of 18 children with elevation of the pre-beta fraction. These experiments suggest (1) decreased stem cell CFU-C, (2) decreased pb CFU-C, and (3) a serum inhibitor that may be contributing to the depressed pb CFU-C.

Adolescent↗
PubMed1978

Pseudomonas infection of the sternum and costal cartilages. Report of three cases.

Pseudomonas osteochondritis of the chest wall and sternum has rarely been reported, but when present it has been extremely difficult to eradicate. Multiple operations to debride the involved areas and use of antibiotics have often been inadequate to control this resistant infection. This report describes our experience with three patients who had the late development of Pseudomonas osteochondritis of the chest wall. The infection occurred following crush trauma, sternotomy for congenital heart disease, and mastectomy and amputation of the upper extremity for carcinoma of the breast. Antibiotic therapy alone and with limited operations was unsuccessful in controlling the infection in all three instances. Eventually, each patient required extensive regional surgical removal of involved bone and cartilage. Complete healing followed. Our experience favors the early wide removal of bony and cartilaginous tissues in the involved region with preoperative and postoperative coverage by appropriate antibiotics. Operative management is detailed.

Humans↗
PubMed1977

Skin-tumor-initiating ability of benzo(a)pyrene-7,8-diol-9,10-epoxide (anti) when applied topically in tetrahydrofuran.

The skin-tumor-initiating abilities of various metabolites of benzo(a)pyrene (BP) were determined in mice by using a two-stage system of tumorigenesis. We previously reported that BP-7,8-dihydrodiol (+/- trans) was approximately as potent as BP, suggesting that it may be a proximate carcinogen, but the alleged ultimate carcinogen of BP [BP-7,8-dihydrodiol-9,10-epoxide (anti)] was a weak tumor initiator (Cancer Lett.2: 115, 1976). Because of its high reactivity, the tumor-initiating ability of the BP-7,8-dihydrodiol-9,10-epoxide (anti) was determined by using acetone, benzene, and tetrahydrofuran (THF) as the solvent vehicles. The 'diol-epoxide' of BP was found to be an effective tumor initiator when applied topically in THF. The effectiveness of the various vehicles for the 'diol-epoxide' was as follows: THF greater than benzene greater than acetone; however, acetone was the best solvent for BP tumor initiation. The BP-9,10-dihydrodiol and BP-3-hydroxy were found to be weak tumor initiators. BP-3-hydroxy was also tested for tumor-promoting ability and was found to be inactive in this capacity.

Acetone↗
PubMed1976

Carcinoma of the colon and rectum. A review of results of surgical treatment in 164 patients.

This report is a retrospective review of the authors' experience with colonic and rectal carcinoma in 164 patients from 1954 to 1968 with a five-year follow-up. The operative approach utilized principles of early vascular isolation, wied-colon and mesenteric reseciton, and minimal tumor manipulation in curative operations; palliative procedures were aggressively employed. Of the 164 patients, 104 with lesions almost equally divided between colon and rectum had resections with curative intent. The overall five-year survival rate after curative resection was 55%, and included eight hospital deaths that were usually related to cardiopulmonary complications. Lymph node involvement appreciably decreased the survival rate from 72% without node involvement to 39% with node involvement. Patients with rectal lesions experienced more favorable results than those with colonic lesions. Palliative procedures in 46 patients enhanced comfort, but few patients survived longer than one year. Wound and anastomotic complications were infrequent.

Adenocarcinoma↗
PubMed1976

Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome).

A 25 year old patient with congenital hypoplastic anemia (Black-fan-Diamond syndrome) is described. This patient was hepatitis-antigen negative, had not received androgens and had a hepatoma develop in a transfusional hemochromatotic liver. Since androgens have been associated with hepatocellular carcinoma, the use of androgenic steroids for other than life-threatening symptoms in this disease should be avoided.

Adult↗
PubMed1976

Inhibition of membrane peroxidation in thalassaemic erythrocytes by 2,3-dihydroxybenzoic acid.

Both iron and precipitated haemoglobin may catalyse the formation of free radicals, which in turn react with the polyunsaturated fatty acids of membranes leading to membrane failure and cell death. 2,3-Dihydroxybenzoic acid (2,3-DHB), a recently identified, orally effective iron-chelating drug, inhibited membrane peroxidation in vitro in H2O2-stressed erythrocytes from patients with beta-thalassaemia major, beta-thalassaemia intermedia, haemoglobin Köln disease and sickle cell disease. We present evidence suggesting that the inhibition of peroxidation is due to ability of 2,3-DHB to scavenge free radicals via quinone formation, a mechanism analogous to that proposed for vitamin E.

Cell Membrane↗
PubMed1976

Platelet dysfunction in vincristine treated patients.

Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions.

Adenosine Diphosphate↗
PubMed1976

Chelation studies with 2,3-dihydroxybenzoic acid in patients with beta-thalassaemia major.

2-3-Dihydroxybenzoic acid was evaluated as a potentially useful, orally effective iron-chelating drug by performing iron balance studies in patients with beta-thalassaemia major. The administration of this substance at 25 mg/kg/d to five patients for 8 d caused an average increase in iron excretion of 4.5 mg/d. When the drug was administered at 25 mg/kg q.i.d. to eight patients for 21 d, iron excretion increased to 6.5 mg/d. Chelation was highly specific for iron with changes in magnesium and calcium excretion being insignificant. The drug was well tolerated with side effects limited to gastrointestinal complaints which ameliorated when the drug was taken with food. These studies provide a rationale for further evaluation of 2,3-dihydroxybenzoic acid in patients with iron overload.

Administration, Oral↗
PubMed1976

Ribosomal RNA: the message or matrix for ribosomal proteins.

The known nucleotide sequence of Escherichia coli 16S ribosomal RNA has been converted to amino acid sequences in all possible ways, and compared to known ribosomal protein sequences. The degree of similarity is precisely what one would expect by chance alone, providing additional evidence that ribosomal proteins cannot be coded for by ribosomal RNA.

Amino Acid Sequence↗
PubMed1976

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen.

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.

Animals↗
PubMed1976

Heme synthesis in hereditary hemolytic anemias: decreased delta-aminolevulinic acid synthetase in hemoglobin Köln disease.

The activities of delta-aminolevulinic acid (ALA) synthetase and ALA dehydratase in cord blood erythrocytes of newborn infants and peripheral blood red cells of patients with beta-thalassemia major, beta-thalassemia intermedia, hemoglobin Köln (Hb Köln) disease, sickle cell anemia, and pyruvate kinase deficiency were studied. The activity of ALA dehydratase did not vary appreciably with the number of immature RBC (reticulocytes and nucleated red blood cells) or the severity of the hemolytic anemia except in pyruvate kinase deficiency. The activity of ALA synthetase was linearly correlated with the number of immature RBC (r=0.974, p is less than 0.001). The ALA synthetase activity was significantly decreased in the RBC of Hb Köln (p is less than 0.01) when compared with the activity in immature RBC of newborns and of patients with pyruvate kinase deficiency, sickle cell anemia, and thalassemia intermedia.

5-Aminolevulinate Synthetase↗