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Biomedical subjects

M Aiken

Publications and source records attributed to M Aiken.

16 recordsLinked to original sources
PubMed2006

The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

Adult↗
PubMed1994

A cluster of tuberculosis among crack house contacts in San Mateo County, California.

In March 1992, a cluster of 89 persons with tuberculosis infection was identified in San Mateo County, California. Thirteen persons (15%), including 11 children, were diagnosed with active pulmonary tuberculosis. All contacts were African Americans who resided in or visited one of two houses used for crack cocaine smoking or dealing. The patient with the index case, a male infected with human immunodeficiency virus, contributed to the transmission of tuberculosis as a transient resident of several dwellings. Public health authorities applied unique intervention methods to control the outbreak, including the use of a mobile health van. Further innovative strategies will be necessary to meet the challenge of this reemerging disease.

Adolescent↗
PubMed1990

Changes in the composition of the hamster zona pellucida after fertilization in vivo but not in vitro.

Hamster zonae pellucidae were obtained from follicular oocytes, superovulated eggs, and eggs fertilized in vivo or in vitro. Zonae were labelled with N-succinimidyl-3(4-hydroxy,5-[125I]iodophenyl)propionate, and compared on single- and two-dimensional SDS-PAGE. Single-dimensional electrophoresis showed considerable differences between zona categories in the amount of label that they incorporated; follicular zonae incorporated the least label and zonae from eggs fertilized in vivo the most. On two-dimensional electrophoresis, polypeptides from 3 of the 4 zona categories migrated into 4 major groups: two of these groups each with Mr 150,000-250,000 were within the Mr range of ZP1, and two others, at Mr 90,000 and 55,000, appeared to be analogous to ZP2 and ZP3, respectively. The fourth zona category (zonae from eggs fertilized in vivo) showed a changed polypeptide profile as well as incorporating the most label; one of the polypeptides, Mr 150,000-250,000, was undetectable, but a train of Mr 70,000-90,000 polypeptides and a discrete polypeptide at Mr 20,000 were new. Since this changed profile did not occur in zonae from superovulated eggs, or in zonae from eggs fertilized in vitro, a synergism between oviductal factors and factors from the spermatozoon or egg, or both, towards the zona in vivo is indicated.

Animals↗
PubMed1986

Isolation and identification of a 23,000-dalton heparin binding fragment from the amino terminus of bovine thrombospondin.

Bovine freeze-thaw lysed platelets were fractionated by dextran sulfate affinity chromatography and a purified protein of 23,000 Da was subsequently obtained by G-75 gel filtration of the 0.5 M NaCl fraction. This protein had an amino terminal sequence of Asn-Arg-Ile-Pro-Glu-Ser-Gly-Gly-Asp-Asn-Ser-Val-Phe-Asp-Ile-Phe-Glu-Leu- Thr-Gly-Ala-Ala-Trp-Lys-, a sequence identical to that reported for human thrombospondin. Thrombin-released platelets, fractionated in an identical manner, yielded a protein of 30,000 Da. Immunoblotting of purified bovine platelet thrombospondin and the 150,000- and 30,000-Da plasmin-generated thrombospondin fragments indicated that polyclonal antisera raised against the 23,000-Da protein cross-reacted with intact thrombospondin and the 30,000-Da fragment but not the 150,000-Da fragment. The 23,000-Da protein possessed weak heparin neutralization activity.

Amino Acid Sequence↗
PubMed1985

Thrombin-elicited contractile responses of aortic smooth muscle.

Human alpha-thrombin at physiologically relevant concentrations of 0.75 to 225 nM (0.01 to 22 clotting units/ml) caused rabbit thoracic aorta to slowly contract in isolated organ baths. Near maximum contractile tension (10% below the irreversible contraction caused by 22 units/ml) was slowly generated by 75 nM alpha-thrombin (8 units/ml) over 18 min and was 50% that of the norepinephrine (NE) control. The initial tonus could only be regained by repeated washing and 60 min equilibration. Tissues were refractory to a second 75 nM alpha-thrombin challenge but responded fully to 1.0 microM NE. Conversion of human alpha-thrombin to nonclotting but estero/amidolytically active gamma-thrombin (less than 0.1% clotting activity) or nitration of the enzyme (1% clotting activity) did not interfere with the contractile activity, whereas chemical conjugates of the parent enzyme at the catalytic site were inactive. Neither atropine, phentolamine, nor indomethacin blocked the thrombin-induced contractions, whereas D-600 was markedly inhibitory. Preincubation of the tissue with inactive forms of thrombin did not prevent the alpha-thrombin-induced response. Removal of the vascular endothelium did not prevent contraction. Aorta preparations with intact endothelium relaxed in the presence of very low concentrations (0.75 to 750 pM) of alpha-thrombin prior to contracting in response to higher concentrations during cumulative dose-response experiments. Our data suggest that catalytically active thrombin forms (alpha- or nonclotting beta- and gamma-thrombins) may have hemostatic functions at the vascular levels in hemostasis.

Animals↗
PubMed1985

Incidence, significance and remission of tubal spasm during attempted hysteroscopic tubal sterilization.

Four hundred three attempted hysteroscopic tubal sterilizations were performed. Tubal spasm was encountered in 37 cases (9.2%) and prevented bilateral placement of tubal plugs in 16 of those cases. There was some evidence that glucagon was associated with a higher rate of remission and that women using barrier birth control methods experienced a lower incidence of tubal spasm. A number of other factors were found to be unrelated to tubal spasm and its remission.

Diazepam↗
PubMed1984

Thrombospondin fragmentation by alpha-thrombin and resistance to gamma-thrombin.

In the presence of 2mM-Ca2+, alpha-thrombin slowly cleaved thrombospondin (Mr 180 000) into 150 000-Mr and 30 000-Mr fragments. In the absence of Ca2+, the platelet glycoprotein was progressively and completely hydrolysed by 3 units of the enzyme/ml to 130 000-Mr, 95 000-Mr and 65 000-Mr fragments. In contrast, the nonclotting enzyme form, gamma-thrombin, did not hydrolyse the platelet protein either in the presence or in the absence of Ca2+, even at 10-fold higher concentrations of enzyme. Protein-interacting regions removed from the catalytic site, like those required for fibrinogen recognition, are necessary for thrombin proteolysis of thrombospondin.

Animals↗
PubMed1984

Antibodies against a 23Kd heparin binding fragment of thrombospondin inhibit platelet aggregation.

Antiserum against a 23Kd heparin binding fragment of thrombospondin inhibits the aggregation of platelets in response to ADP, collagen or thrombin. The antiserum inhibits the secretion-dependent second phase, but not the primary phase of aggregation of platelets responding to ADP. Although immune serum added during the second phase of ADP-induced aggregation causes some inhibition of secretion, it also causes reversal of aggregation to the level produced during primary aggregation. Since thrombospondin is the endogenous lectin of human platelets, these results support the conclusion that the endogenous lectin mediates, at least in part, the secretion-dependent aggregation of platelets. Our data suggest that the region of thrombospondin which contains the heparin binding domain(s) present in the 23Kd fragment play(s) a critical role in secretion-dependent aggregation of platelets.

Adenosine Diphosphate↗
PubMed1984

Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10(-7) mol/L and 1 X 10(-6) mol/L during infusion of 650 and 1,000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1,000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

Bone Marrow↗