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Biomedical subjects

D A Collins

Publications and source records attributed to D A Collins.

At least 19 recordsLinked to original sources
PubMed2000

Problems with primate sex ratios.

Birth sex ratios of baboons in Gombe National Park, Tanzania, show an overall male bias of ca. 20%, but there is no obvious explanation for this trend. Individual females did not alter their sex ratios according to persistent levels of local resource competition. Sex ratios showed an unexpected relationship between age and rank: subordinate females had more sons when they were young; dominant females had more sons when they were old. The sex ratio of low-ranking females also varied with the severity of environmental conditions during pregnancy. Our findings suggest that mammalian sex ratios might be the product of more complex processes than is generally recognized or that sex-determining mechanisms impose sufficient constraints to prevent adaptive variation in all contexts.

Animals↗
PubMed2000

Synthesis and characterization of nido-carborane-cobalamin conjugates.

Three vitamin B12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B12 binding capacity assay. When compared with 57Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.

Boron Compounds↗
PubMed2000

Biodistribution of radiolabeled adenosylcobalamin in patients diagnosed with various malignancies.

OBJECTIVE: To study the biodistribution of a vitamin B12 analog, indium In 111-labeled diethylenetriaminepentaacetate adenosylcobalamin (In 111 DAC), in patients recently diagnosed as having primary or recurrent malignancy. PATIENTS AND METHODS: Thirty patients (14 women and 16 men) with radiographically or clinically diagnosed breast, lung, colon, sarcomatous, thyroid, or central nervous system malignancies were studied prior to definitive surgery or biopsy. A maximum of 650 microCi (2.2 microg) of In 111 DAC was administered intravenously. Vitamin B12 and folate levels were determined prior to injection. Serum clearance and urinary and stool excretion of the tracer were measured. Images were routinely obtained at 0.5, 3 to 5, and 20 to 24 hours after injection. Biodistribution of In 111 DAC was determined by computer analysis of regions of interest. RESULTS: Serum T1/2 clearance was 7 minutes. Average urinary and stool excretion of the injected dose over 24 hours was 26.1% and 0.4%, respectively. The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands. The average tumor uptake of the injected dose was 2% at 30 minutes and 1.5% at 24 hours. High-grade primary and metastatic breast, lung, colon, thyroid, and sarcomatous malignancies were all imaged at 3 to 5 hours after injection. Central nervous system tumors and advanced metastatic prostate cancer were best identified at 24 hours. Mammographically occult, palpable, and nonpalpable breast cancers were delineated by In 111 DAC. Low-grade malignancies as well as early skeletal metastatic disease were not effectively imaged by the vitamin B12 tracer. Patients with elevated baseline vitamin B12 or those concurrently taking corticosteroids appeared to have optimal visualization of their malignancies. CONCLUSION: Vitamin B12 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.

Adult↗
PubMed1999

5'-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis patients.

OBJECTIVES: To evaluate measurements of serum and synovial fluid 5'-nucleotidase (5'N) activity as a marker of general and local inflammation in arthritis, and to resolve a contradiction in the literature as to whether or not the activity of 5'N in the synovial fluids of rheumatoid arthritis (RA) patients is raised in comparison with that in the synovial fluids of other arthritis patients. METHODS: Assays for 5'N were carried out in the presence of inhibitors of other phosphatases, AMP deaminase and of 5'N itself. RESULTS: The 5'N activity in the synovial fluid of RA patients was both significantly higher (mean 1.7-fold) and had a greater variance than that in the synovial fluids of other arthritis patients, and the contradiction in the literature was resolved. There was a strong correlation between the 5'N activity in the sera of RA patients and their erythrocyte sedimentation rate. There was no significant correlation between the 5'N in the serum and synovial fluid for the RA patients, in marked contrast to the strong correlation between the two 5'N activities shown by the osteoarthritis patients. The 5'N activity was greater in the synovial fluid than in the serum for virtually all the patients, showing that it was being made locally. CONCLUSIONS: The 5'N activity in the serum (which came mostly from the liver) could be used as a marker of general inflammation, whereas the 5'N in the synovial fluid was mostly produced locally, and could be used as a marker of joint inflammation, particularly for the RA patients.

5'-Nucleotidase↗
PubMed1999

Tumor imaging via indium 111-labeled DTPA-adenosylcobalamin.

Vitamin B12 is essential for life. Lack of it results in pernicious anemia and death. Conversely, the demand for vitamin B12 increases in rapidly dividing tumors. This is secondary to the direct involvement of vitamin B12 in mitochondrial metabolism as well as its indirect role in the production of thymidylate and S-adenosylmethionine. The latter 2 substances are needed for DNA synthesis and cellular methylation reactions, respectively. Novel radiolabeling of adenosylcobalamin has proven to be useful in the imaging of transplanted and spontaneous tumors in animals. Herein, we describe what we believe to be the first human to have imaging with conventional gamma cameras of vitamin B12 metabolism in a breast tumor.

Breast Neoplasms↗
PubMed1998

Preventing and reducing alcohol and other drug use among high-risk youths by increasing family resilience.

This study examines the effects of a community-based program designed to delay onset and reduce the frequency of alcohol and other drug (AOD) use among high-risk youths, ages 12 to 14, through strengthening family resilience. It is part of a larger five-year demonstration project funded by the Center for Substance Abuse Prevention (CSAP). The program was implemented in multiple church communities in rural, suburban, and inner-city settings. Program components of this study included parent or guardian and youth training, early intervention services, and follow-up case management services. The results show that the program produced positive direct effects on family resilience. The evaluation also found positive moderating effects on delayed onset of alcohol and other drug use and frequency of alcohol and other drug use among youths in the form of conditional relationships with changes in those family resilience factors that were targeted by the program.

Adolescent↗
PubMed1997

Schistosoma mansoni infection in a natural population of olive baboons (Papio cynocephalus anubis) in Gombe Stream National Park, Tanzania.

Infection with Schistosoma mansoni was studied in 5 troops of olive baboons (Papio cynocephalus amubis) in Gombe Stream National Park, Tanzania. Three troops were infected with S. mansoni. An aggregated distribution of parasites was observed among hosts. Troop membership was found to be the most significant factor influencing parasite prevalence. Age and reproductive status had no significant effect, but there was a trend for males to acquire higher levels of infection. However, age-prevalence curves showed a high infection in young baboons declining in the older baboons. Behavioural components of exposure--as measured in water-contact pattern--may be related to parasite burden. A 'peak shift' between infection in different age-classes in the different troops was observed: troops with higher schistosome prevalences displayed an earlier peak in prevalence of infection. The baboon troop with the most contact with people showed highest prevalence of infection possibly due to longer exposure to the parasite than the other troops and/or higher host density.

Age Distribution↗
PubMed1997

Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis.

This analysis was designed to characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin (OPC-17,116) in patients with acute bacterial exacerbations of chronic bronchitis (ABECB). The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age, who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin, 200, 400 or 600 mg, each administered once daily for 14 days. Plasma samples for drug assay (typically eight per subject; four samples on either day 3, 4 or 5, plus troughs on other clinic visit days), were obtained during treatment. Population pharmacokinetic analysis was accomplished using iterative two-stage analysis. Cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the time (in days) taken to eradicate each bacterial strain. Population pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure, probability of clinical cure, and time to eradication. Grepafloxacin plasma concentration profiles were best fitted by a pharmacokinetic model with first-order absorption following a lag time between administration of the dose and onset of systemic absorption. All three measures of response were strongly related to the 24 h AUIC (AUC/MIC). At an AUIC of <75, the percent probability of clinical cure was 71%; at an AUIC of 75-175, it was 80% (P < 0.05) and at an AUIC of >175, it was 98% (P < 0.01). In conclusion, antibacterial response for grepafloxacin in ABECB patients was highly related to AUIC; values of <75 appear inadequate and values of >175 were optimal.

Administration, Oral↗
PubMed1997

Bilateral axillary lymph node uptake of radiotracer during lower extremity lymphoscintigraphy.

Lymphoscintigraphy is a useful technique for the evaluation of lymphatic function in the presence of limb swelling. The authors report a case where proximal lower limb and genital swelling in a 23-yr-old man was investigated by lymphoscintigraphy. The patient had a history of previous surgery and subsequent infection in the affected groin. Lower limb lymphoscintigraphy showed features of an unusual lymphatic drainage pattern that most likely represented adaptation to chronic lymphatic insufficiency. The drainage pattern was characterized by marked dermal backflow pattern, aberrant lymph node uptake in the abdomen and chest and unexpected avid radiotracer uptake in the axillae bilaterally.

Adult↗
PubMed1997

Transcobalamin II receptor imaging via radiolabeled diethylene-triaminepentaacetate cobalamin analogs.

UNLABELLED: Rapidly dividing cells up-regulate the number of transcobalamin II receptors during DNA replication. We have developed diethylene-triaminepentaacetate (DTPA) cobalamin analogs for the purpose of imaging transcobalamin II receptors in malignant and nonmalignant tissue. METHODS: Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs were synthesized. In vitro binding of the analogs to the transcobalamin proteins was assessed by the unsaturated vitamin B12 binding capacity assay and compared to DTPA and cyanocobalamin. The biodistribution of the 111In-DTPA cobalamin analogs was measured at 24 hr after injection into sarcoma-bearing mice and non-tumor-bearing mice and pigs. RESULTS: Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs and DTPA were 94.0%, 90.4%, 66.4%, and 3.6%, respectively, as efficient in binding to the transcobalamin proteins when compared to cyanocobalamin. At 24 hr after administration, the cobalamin analogs had 5-17 times and 20-29 times, respectively, the amount of uptake within the resected tissue samples and transplanted sarcomas when compared to 111In-DTPA. CONCLUSION: The radiolabeled DTPA cobalamin analogs are biologically active. Preliminary animal studies suggest that the analogs could be effective in vivo transcobalamin II receptor imaging agents.

Animals↗
PubMed1997

Reduction in heart rate variability in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether heart rate variability and cardiovascular reflex tests are abnormal in patients with systemic lupus erythematosus (SLE). METHODS: We measured heart rate variability (24 h ambulatory recordings), and used baroreflex sensitivity testing and cardiovascular reflex tests in a cross sectional, case-control study. Those taking drugs with cardiovascular activity were excluded. RESULTS: Determination of heart rate variability was simple to perform, well tolerated, and found to be reduced in the patients with lupus, but not strongly related to disease activity or duration. CONCLUSION: This may reflect underlying autonomic dysfunction; longitudinal studies will determine full clinical relevance.

Adult↗
PubMed1996

Intestinal parasite burden in five troops of olive baboons (Papio cynocephalus anubis) in Gombe Stream National Park, Tanzania.

A cross-sectional parasitological study of a population of wild olive baboons (Papio cynocephalus anubis), consisting of 5 troops, was conducted in Gombe Stream National Park. Baboons were individually recognizable. Information on age, sex, troop membership, reproductive status, social rank and life-history of each individual baboon could be related to parasite infection. Seven helminth taxa and 2 protozoan taxa were found. All baboons were parasitized by at least 1 taxon. Distributions of helminths were aggregated among hosts. There were significant differences among troops in the prevalence of all but 2 of the recorded helminths. Age had a significant impact on the prevalence and intensity of Strongyloides sp. No significant effect of sex on the prevalence of infection could be detected. There was some indication that female reproductive status was related to Trichuris egg output. In contrast to a previous study, no significant correlations between parasite infection and social rank could be found. Troop membership constituted the predominant factor contributing to heterogeneity of prevalence of infection. This suggests that spatial location and/or genetics may be important in determining levels of parasite infection.

Age Factors↗
PubMed1996

Prostatic calcifications detected on Tc-99m MDP bone scan mimicking bone metastasis.

Uptake of Tc-99m MDP tracer was noted within prostatic calcifications in a 48-year-old man with no known malignancy who underwent a three-phase bone scan for left knee and thigh pain. Routine anterior and posterior views of the pelvis demonstrated focal tracer uptake within the right pubic bone, which mimicked a metastatic lesion. Additional imaging showed the uptake to be extraosseous and localized within the prostate in a distribution similar to the extensive prostatic calcifications seen on the corresponding plain film and computed tomography examinations of the pelvis. This unusual presentation illustrates another potential artifact that may be present in scintigraphic bone imaging of the pelvis.

Bone Neoplasms↗
PubMed1996

Favourable outcome of scleroderma renal crisis.

Severe hypertension and rapidly progressive acute renal failure is a well recognized complication of scleroderma, often referred to as the renal crisis, and widely thought to cause irreversible deterioration in renal function. With the advent of angiotensin-converting-enzyme inhibitors (ACE-I) the outlook for patients with this condition has dramatically improved. We report here one such patient.

Acute Kidney Injury↗
PubMed1995

Reproductive constraints on aggressive competition in female baboons.

Competitive interaction between females of same social group is characteristic of most primate species. In Old World monkeys, females of high social rank maintain priority of access to scarce resources and harass low-ranking companions. But different field studies have found differing correlations between female dominance and reproductive success: several populations show an advantage of rank whereas others do not. Although such variation may reflect divergent levels of predation, food availability or social stress in different environments, female competitive ability may also be balanced by significant reproductive costs and thus be subject to strong stabilizing selection. We report here that high-ranking female baboons (Papio cynocephalus anubis) at Gombe National Park, Tanzania, enjoy shorter interbirth intervals, improved infant survival, and accelerated maturation of their daughters. These advantages, however, are countered by a significantly higher probability of miscarriage, and a proportion of high-ranking females suffer from reduced fertility.

Abortion, Veterinary↗