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Biomedical subjects

C Collins

Publications and source records attributed to C Collins.

At least 127 records · Page 7Linked to original sources

Samarium-153-EDTMP biodistribution and dosimetry estimation.

Fifty-two patients were treated with single doses of 153Sm-EDTMP in a Phase I escalating dose protocol for palliation of bone pain from metastatic prostate carcinoma. Samarium-153 (T1/2 46.3 hr), maximum beta-particle energies 810 keV (20%), 710 keV (30%), 640 keV (50%), gamma photon 103 keV (28%), was complexed to the tetraphosphonate chelate, EDTMP. Five groups of patients were treated at doses of 1.0, 1.5, 2.0, 2.5, and 3.0 mCi/kg to evaluate toxicity from treatment. Patients were screened prior to treatment and followed after treatment with 99mTc-MDP bone scans. Biodistribution data on this group of patients were acquired and showed rapid uptake of 153Sm-EDTMP into bone with complete clearance of nonskeletal radiotoxicity by 6-8 hr. Also included are complete sets of dosimetry estimations on an additional seven patients who received 0.5 mCi/kg 153Sm-EDTMP Ca++ as part of a multiple dose therapy trial. Estimated radiation absorbed doses to bone surfaces averaged 25,000 mrad/mCi (6686 Gy/MBq), and urinary bladder doses averaged 3600 mrad/mCi (964 Gy/MBq).

Bone Neoplasms↗

Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial.

Samarium-153-ethylenediaminetetramethylene phosphoric acid (EDTMP), a bone-seeking radiopharmaceutical, was given to prostate cancer patients in a dose escalation protocol for pain palliation to determine the maximally tolerated dose. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg). Pain response after treatment was assessed as well as hematologic and serum chemistry parameters. Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.

Aged↗

Evaluation of routine diabetes and lipid screening after age 35 in candidates for or current users of oral contraceptives.

OBJECTIVE: To evaluate the efficacy of a diabetes and lipid screening program in women aged 35 or older who either were currently using a low-estrogen-dose oral contraceptive (OC) (0.03-0.04 ethinyl estradiol) or who desired to initiate low-dose OC therapy after using a non-OC method or following a recent pregnancy. METHODS: Healthy women with no history of abnormal glucose tolerance, hypertension, or hyperlipidemia aged 35 years and older were routinely screened for diabetes (fasting and 2-hour values after 75 g glucose) and dyslipidemia (fasting total cholesterol, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol, and triglycerides). Three groups of women were studied: women currently using low-dose OCs (OC group), women desiring to change to OC therapy (non-OC group), and women within 3 months post-pregnancy (postpartum group). RESULTS: The three groups were similar in age, parity, body mass index (BMI), and mean arterial pressure. The mean months of contraceptive use were not different between the OC group (30.2 months; 95% confidence interval [CI] 26.6-33.8) and the non-OC group (38.4 months; 95% CI 32.0-44.8). The mean fasting serum glucose, after adjusting for age and BMI, was significantly lower in the OC group (82.4 +/- 9.4 mg/dL) than in the non-OC and postpartum groups (87.2 +/- 12.5 and 86.8 +/- 13.0 mg/dL, respectively; P = .01). After adjustments, no differences between the groups were found in the 2-hour post-glucose levels, triglycerides, or HDL or LDL cholesterol levels. The non-OC group was found to have a significantly lower total cholesterol level (188.7 +/- 32.4 mg/dL) than the OC and postpartum groups (202.7 +/- 38.1 and 204.4 +/- 41.0 mg/dL; P = .02) after adjusting for age and BMI. This association lost its significance after applying multiple range tests, maintaining an alpha error of 0.05. CONCLUSION: The absence of significant adverse metabolic markers in longer-term OC users over the age of 35, in comparison to similar-age control groups, does not support the routine use of lipid and diabetes screening before initiating or during the use of low-dose OCs.

Adult↗

The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments.

The development and testing of a multidimensional instrument to assess the reactions of family members caring for elderly persons with physical impairments, Alzheimer's disease, and cancer is reported. Forty items were administered to a sample of 377 caregivers of persons with physical impairments and Alzheimer's disease. Five dimensions of caregivers' reactions were identified through exploratory factor analysis. Using confirmatory factor analysis on an independent sample (N = 377), these dimensions were tested for factorial invariance across spouse and nonspouse caregivers and between caregivers of persons with cancer and those caring for persons with Alzheimer's disease. The subscales also had a high level of factorial invariance across a three-wave panel study (N = 185). The subscales appeared consistent with first order tests of construct validity.

Aged↗

Squamous cell carcinoma of the cervix: HPV 16 and DNA ploidy as predictors of survival.

In this study, the hypothesis that DNA ploidy and the presence of HPV 16 and HPV 18 DNA affects survival of patients with squamous cell carcinoma of the cervix was tested. Archival paraffin blocks from biopsy and surgical specimens were obtained from 127 women diagnosed in 1977-1984. Determination of DNA ploidy was by flow cytometry and HPV 16 and HPV 18 DNA status by polymerase chain reaction with subsequent dot-blot hybridization. For each patient, age, stage, treatment modality, and 5-year survival were correlated with ploidy and HPV status. HPV 16 DNA was present in 53% of the tumors. HPV 18 was not detected in this population. HPV 16 DNA was found twice as often in Stages IB and IIA than in advanced-stage disease (III and IV). These advanced-stage tumors were more commonly aneuploid. Neither HPV status nor DNA ploidy were predictive of survival for any stage of disease or therapeutic modality.

Adult↗

The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.

We have identified and sequenced cDNA clones that encode for the human beta-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human beta-subunit protein is 90% identical to the bovine beta-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the beta-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p 16.3, in the pathogenesis of Huntington disease.

3',5'-Cyclic-GMP Phosphodiesterases↗

Exclusion of DNA changes in the beta-subunit of the c-GMP phosphodiesterase gene as the cause for Huntington's disease.

To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.

3',5'-Cyclic-GMP Phosphodiesterases↗

Delineation of a 50 kilobase DNA segment containing the recombination site in a sporadic case of Huntington's disease.

No detectable rearrangements involving chromosome 4p16.3 have been observed in patients with Huntington's disease (HD). New mutations for HD could involve structural alterations which might aid the localization of the defective gene. We have reinvestigated a well documented sporadic case of HD. DNA haplotyping with markers between D4S10 and the telomeric locus D4S141 reveals a recombination event in one chromosome of the sporadic HD patient. The site of recombination maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based on the extremely low HD mutation rate and significantly decreased recombination in the distal region of 4p, we hypothesize a direct link between the site of the recombination and HD in this patient.

Adult↗

Surveying University of Arizona students' health.

The authors sampled more than 600 University of Arizona students to determine how student attitudes, beliefs, and practices should be considered by healthcare personnel in planning campus health education programs. The survey found that students worried more about diet, exercise, and weight than they did about more serious health problems and that, although generally positive and optimistic, the students frequently felt anxious and overwhelmed. Two thirds of the students were sexually active, 74% of those who were active used various contraceptive methods. More than three quarters of those surveyed indicated they currently drank alcoholic beverages; one quarter of the drinkers said they frequently downed three or more drinks on one occasion, and 44% of the drinkers reported driving while under the influence of alcohol.

Arizona↗

Radiochemical assay to measure the biofilm produced by coagulase-negative staphylococci on solid surfaces and its use to quantitate the effects of various antibacterial compounds on the formation of the biofilm.

A firmly adherent mass of slime plus organisms (biofilm) accumulates on the sides of culture tubes when some strains of coagulase-negative staphylococci are grown in a chemically-defined medium containing [14C]glucose. This mass was washed (to remove labelled medium) and then counted after adding scintillation fluid. Organisms from the liquid culture were also washed and counted to check that [14C]glucose had been utilised to label the bacteria. Nine strains were examined in this way, and the results were compared with those obtained with four older techniques for recognising slime production or adherent bacteria. The new method is quick, and has advantages of reproducibility and good discrimination between strains; there was a 15-fold difference in counts in the biofilm between slime-producing and non-producing strains respectively. With the new radiolabel assay, the effects of several antibacterial compounds on the build-up of the biofilm were investigated with four slime-producing strains. Tunicamycin, chloramphenicol and 5-fluorouracil, at levels below their minimum growth-inhibitory concentrations, each greatly diminished biofilm formation; several other drugs had less effect.

Adenosine Triphosphate↗

Foetal radiation dose in radiotherapy for breast cancer.

Management of breast cancer during pregnancy is complicated by the high risks of abortion and foetal malformation from the use of radiotherapy and chemotherapy. A case of breast cancer during pregnancy, treated with radiotherapy, and the estimated foetal dose is reported.

Adult↗

Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma.

PURPOSE: Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity. PATIENTS AND METHODS: In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5-day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20). RESULTS: In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%). CONCLUSION: These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy.

Adult↗

Systemic distribution of wear debris after hip replacement. A cause for concern?

The production of particulate wear debris is a recognised complication of joint arthroplasty, but interest has concentrated on local tissue reactions and a possible association with implant loosening. The fate of wear products in the body remains unknown, although some of the metals used in the construction of orthopaedic implants are known to have toxic and oncogenic properties. We report histological and electron-microscopic evidence from two cases which shows that metallic debris can be identified in the lymphoreticular tissues of the body distant from the hip some years after joint replacement. The increase in the use of total arthroplasty in younger patients, the development of new alloys and the use of porous coatings must raise concern for the long-term effects of the accumulation of wear debris in the body.

Aged↗

The genomic organization of a novel regulatory myosin light chain gene (MYL5) that maps to chromosome 4p16.3 and shows different patterns of expression between primates.

Myosin participates in a varying repertoire of cellular functions ranging from cytokinesis, receptor capping and secretion to sarcomere contraction. In vertebrates this functional complexity is achieved through the regulated expression of gene families encoding isoproteins for each of the myosin subunits. We report here the identification and characterization of a gene (MYL5) that encodes a novel regulatory myosin light chain isoprotein and maps 700 kb from the human chromosome 4p telomere. Identical cDNAs have been isolated from human adult retina and fetal muscle cDNA libraries. A full length 519 bp open reading frame was identified in the cDNA sequence encoding a predicted protein of 173 residues. Sequence analysis of a 5.6 kb genomic region that encodes these cDNAs revealed the presence of 7 exons which span 4 kb. Expression of this gene has been detected in human adult retina, cerebellum, basal ganglia and fetal skeletal muscle. Whereas Northern analysis fails to detect transcription of this gene in human adult skeletal muscle it reveals an abundant transcript in monkey skeletal muscle. Phylogenetic comparison of the predicted proteins primary structure to those of related myosin light chains from Drosophila, rat and human reveal evolutionarily conserved structural motifs important for both calcium binding and phosphorylation.

Adult↗

Isolation and characterization of new highly polymorphic DNA markers from the Huntington disease region.

The defect causing Huntington disease (HD) has been mapped to 4p16.3, distal to the DNA marker D4S10. Subsequently, additional polymorphic markers closer to the HD gene have been isolated, which has led to the establishment of predictive testing programs for individuals at risk for HD. Approximately 17% of persons presenting to the Canadian collaborative study for predictive testing for HD have not received any modification of risk, in part because of limited informativeness of currently available DNA markers. Therefore, more highly polymorphic DNA markers are needed, which will further increase the accuracy and availability of predictive testing, specifically for families with complex or incomplete pedigree structures. In addition, new markers are urgently needed in order to refine the breakpoints in the few known recombinant HD chromosomes, which could allow a more accurate localization of the HD gene within 4p16.3 and, therefore, accelerate the cloning of the disease gene. In this study we present the identification and characterization of nine new polymorphic DNA markers, including three markers which detect highly informative multiallelic VNTR-like polymorphisms with PIC values of up to .84. These markers have been isolated from a cloned region of DNA which has been previously mapped approximately 1,000 kb from the 4p telomere.

Chromosomes, Human, Pair 4↗