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Biomedical subjects

C Ramsey

Publications and source records attributed to C Ramsey.

18 recordsLinked to original sources

Use of assisted reproductive technologies in the propagation of rhesus macaque offspring.

The assisted reproductive technologies (ARTs) as tailored to the production of rhesus monkeys at the Oregon National Primate Research Center (ONPRC) are described. Efficient fertilization of mature oocytes recovered by aspiration from females subjected to follicular stimulation was achieved with fresh or frozen sperm by intracytoplasmic sperm injection (ICSI). Embryo development to the early cleavage stage occurred at high frequency. Cryopreserved embryos showed high postthaw survival and were also transferred in efforts to establish pregnancies. Three methods of transfer were evaluated, two involving embryo placement into the oviduct, laparoscopy and minilaparotomy, and a nonsurgical, transcervical approach that resulted in uterine deposition. Early cleaving embryos (Days 1-4) were transferred into the oviducts of synchronized recipients with optimal results and pregnancy rates of up to 36%. Pregnancy rates were similar when two fresh or frozen embryos were transferred (28- 30%), although more than two embryos had to be thawed to compensate for embryo loss during freeze-thawing. Normal gestational lengths, birth weights, and growth curves were seen with ART-produced infants compared with infants produced by natural mating in the timed mated breeding (TMB) colony at the ONPRC. In 72 singleton pregnancies established following the transfer of ART-produced embryos, the live-birth rate, at 87.5%, was statistically identical to that for the TMB colony. Further development of the ARTs should result in increasing use of these techniques to augment conventional approaches to propagating monkeys, especially those of defined genotypes.

Animals↗

Comparison of CT and MRI in the pre-operative staging of rectal adenocarcinoma and prediction of circumferential resection margin involvement by MRI.

OBJECTIVE: It has been suggested that MRI may be used as the sole modality of choice in pre-operative staging in rectal cancers. Knowledge of tumour stage and a threatened Circumferential Resection Margin (CRM) pre-operatively are essential for planning neo-adjuvant therapy and as predictors of local recurrence. At present most units utilize CT scanning to assess these parameters. The aim of our study was two fold: firstly to examine the accuracy of preop CT and MRI staging of rectal cancers compared with final histology and secondly to assess the accuracy of MRI in predicting penetration of the mesorectal envelope (ME). PATIENTS AND METHODS: All patients with biopsy proven rectal adenocarcinoma underwent thin slice MRI and CT scan pre-operatively. Forty-seven patients have been prospectively entered into the study: 24 male (median age 68 years; range 38-91 years). Eleven patients were unsuitable for surgery leaving 36 patients available for study. RESULTS: CT correctly staged patients with T1/T2 rectal cancers more often than MRI (77% vs. 43%, P = 0.226). Patients with T1/T2 tumours were overstaged more often by MRI compared with CT (54% vs. 23%, P = 0.226). A greater proportion of patients with T3 tumours were correctly staged by MRI than CT (76% vs. 41%, P = 0.08); and more T3 disease was understaged by CT than MRI (54 vs. 18%, P = 0.032). CT and MRI staged T4 disease equally. In the assessment of mesorectal envelope integrity, MRI had a sensitivity of 80% and a specificity of 84%. The positive predictive value was 44% and the negative predictive value 96%. CONCLUSIONS: These results suggest significant differences between accurate pre-operative "T" staging by CT and MRI for rectal cancer. MRI has the potential however, to accurately assess mesorectal envelope invasion. Further analysis is required to assess whether MRI can be used as the sole modality in pre-operative staging of rectal cancers.

Adenocarcinoma↗

Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms.

Previous studies have found that constituents in tobacco inhibit both forms of the enzyme monoamine oxidase (MAO-A and MAO-B). This enzyme is important in the breakdown of the amine neurotransmitters, including dopamine, which is thought to mediate the reinforcing effects of nicotine and contribute to tobacco dependence. To further examine the relationship between cigarette smoking, smoking cessation and MAO, we measured platelet MAO-B activity in 16 smokers before and after being switched to smoking denicotinized cigarettes; in a subset of six subjects who subsequently quit-smoking, MAO-B activity was also measured at 1 and 4 weeks following cessation. Smoking cessation treatment was provided in an open-label format, and included nicotine skin patch treatment in conjunction with oral mecamylamine (a nicotinic antagonist) and neostigmine (a peripherally acting acetylcholinesterase inhibitor, administered to counteract constipation experienced from mecamylamine). Results showed that smoking behavior, indexed by expired air carbon monoxide levels, was negatively correlated with platelet MAO-B activity prior to smoking cessation. Moreover, MAO-B activity significantly increased by approximately 100% at 4 weeks after quitting smoking. However, little or no recovery occurred within the first week of abstinence, suggesting that the constituents in tobacco responsible for MAO inhibition may have half-lives of several days. Thus, if relapse to smoking is due in part to withdrawal from the MAO-inhibiting effects of tobacco, this effect likely occurs more than 1 week after quitting. Additionally, low baseline MAO-B activity significantly predicted the intensity of withdrawal symptoms reported upon switching to the denicotinized cigarettes as well as after smoking cessation. These results support the view that MAO inhibition from non-nicotine constituents in cigarette smoke is relevant to tobacco dependence and that continued investigation of the potential use of MAO inhibitors in smoking cessation treatment is warranted.

Administration, Cutaneous↗

Performance-improvement strategies can reduce costs.

Hospitals continue to be challenged to reduce costs while providing high-quality care. Cost-reduction methods that hospitals can use successfully include cost data, interdisciplinary approaches, benchmarking, clinical pathways, physician profiling, and case management. Cost reduction also can be achieved through performance inprovement. One performance-improvement-strategy is the FOCUS-PDCA model. The letters in the model's name refer to the following steps: Find a process that needs improvement, Organize a team that knows the process, Clarify current knowledge of the process, Understand the process and learn the causes of the variation, Select the improvement opportunities, Plan the change, Do, Check the results, and Act by implementing the change. The FOCUS-PDCA model was used by an East Texas regional hospital to reduce the costs relaed to cholecystectomy surgeries performed there.

Benchmarking↗

GPI 6150 prevents H(2)O(2) cytotoxicity by inhibiting poly(ADP-ribose) polymerase.

GPI 6150 (1,11b-dihydro-[2H]benzopyrano[4,3,2-de]isoquinolin-3-one) is a novel inhibitor of poly(ADP-ribose) polymerase (PARP). It has demonstrated efficacy in rodent models of focal cerebral ischemia, traumatic brain injury, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine damage to dopaminergic neurons, regional myocardial ischemia, streptozotocin-induced diabetes, septic shock, and arthritis. Here we report the structure of GPI 6150, its enzymatic characteristics, and biochemical property in cytoprotection. As a competitive PARP inhibitor (K(i) = 60 nM), GPI 6150 protected the P388D1 cells against hydrogen peroxide cytotoxicity, by preventing PARP activation and the depletion of NAD(+), the substrate for PARP. To address the concerns of potential side effects of PARP inhibition, we tested GPI 6150 and found it had no effect on the repair and expression of a plasmid DNA damaged by N-methyl-N'-nitro-N-nitrosoguanidine. Neither did it affect dehydrogenases with NAD co-enzyme. GPI 6150 was much less potent to inhibit mono-ADP-ribosyltransferase. There was no selectivity for GPI 6150 between PARP isozymes. These attributes render GPI 6150 a useful tool to probe the functions of PARP.

ADP Ribose Transferases↗

Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral problem afflicting 5-10% of children and adolescents and persisting into adulthood in 30-50% or more of cases. Family, twin, and adoption studies suggest genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and hyperactivity. Because stimulant intervention is effective in reducing ADHD symptoms in about 70-80% of cases, molecular genetic investigations of genes involved in dopamine regulation are currently underway by many groups. In a case control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and colleagues found an increase of a 7-repeat variant of a 48-bp VNTR in exon 3 among ADHD subjects compared to controls. Swanson and colleagues replicated this finding in a sample of 52 ADHD probands and their biological parents using a haplotype relative risk analysis. Here, we describe linkage investigations of the VNTR and ADHD in affected sibling pair (ASP) families and singleton families using both the transmission disequilibrium test (TDT) and a mean test of identity-by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is differentially transmitted to ADHD children (P = 0.03) while the mean test revealed no evidence of increased IBD sharing among ASPs. In the current sample, the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of the allele estimated under a model described by Risch and Merikangas.

Adult↗

Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models.

Although immunosuppressant immunophilin ligands promote neurite outgrowth in vitro, their neurotrophic activities are clearly independent of their immunosuppressive activity. In the present report, a novel nonimmunosuppressive immunophilin ligand, GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate+ ++) is described. In vitro, GPI-1046 bound to FK506 binding protein-12 and elicited neurite outgrowth from sensory neuronal cultures with picomolar potency with maximal effects comparable to nerve growth factor. In vivo, GPI-1046 stimulated the regeneration of lesioned sciatic nerve axons and myelin levels. In the central nervous system, GPI-1046 promoted protection and/or sprouting of serotonin-containing nerve fibers in somatosensory cortex following parachloroamphetamine treatment. GPI-1046 also induced regenerative sprouting from spared nigrostriatal dopaminergic neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice or 6-hydroxydopamine (6-OHDA) toxicity in rats. The rotational abnormality in 6-OHDA treated rats was alleviated by GPI-1046. These neurotrophic actions in multiple models suggest therapeutic utility for GPI-1046 in neurodegenerative diseases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The microbiology and therapy of acute pelvic inflammatory disease in hospitalized patients.

We examined microbial isolates from the endocervical and peritoneal cavity of 30 women hospitalized with acute PID. Patients were randomly assigned to one of two antibiotic regimens: amoxicillin, 6 gm by mouth every 24 hours, or aqueous penicillin G, 30 million units and gentamicin, 180 to 240 mg intravenously every 24 hours. We measured response by quantifying physical examination findings. Neisseria gonorrhoeae was isolated from the cervix of 24 patients (80%) and from the peritoneal cavity of 10 (33%). Other peritoneal isolates included Enterobacteriaceae in five patients, Ureaplasma urealyticum in five, Mycoplasma hominis in six, and Chlamydia trachomatis in three. Bacteroides melaninogenicus, the most frequent anaerobe, was isolated in 11 cases. Bacteroides fragillis was not isolated from any specimen. The cure rates were the same for both regimens: three patients failed on each. Four women required total abdominal hysterectomy and unilateral or bilateral salpingo-oophorectomy.

Adolescent↗

Pelvic colonization with Actinomyces in women using intrauterine contraceptive devices.

Recent reports suggest a relationship between intrauterine contraceptive device (IUD) use and colonization or infection of the genital tract with Actinomyces species. This prospective, case-controlled study was designed to determine the incidence of colonization or infection with Actinomyces in IUD users. None of 50 control patients and four of 50 study patients (8%) had Actinomyces identified. None of the patients with positive results had symptomatic pelvic infection. Cervical cytology was effective in detecting each of the four study patients with positive results. It appears that the presence of any type of IUD is a major predisposing factor to colonization with Actinomyces.

Actinomycosis↗

Tuberculous mediastinal lymphadenitis in the adult.

The authors present the roentogenological findings and response to treatment of 10 patients with tuberculous mediastinal lymphadenitis (TML). The clinical presentation is usually nonspecific except for the positive tuberculin skin test. The roentgenographic appearance varies but very often includes right tracheobronchial involvement. Tissue diagnosis is often necessary to establish the diagnosis. Since the epidemiology of tuberculosis is shifting, TML will be encountered more frequently in the adult.

Adolescent↗

Chronic Ureaplasma urealyticum and Mycoplasma hominis infections of central nervous system in preterm infants.

In a prospective study of meningitis in 100 predominantly preterm infants, Ureaplasma urealyticum was isolated from the cerebrospinal fluid (CSF) of 8 and Mycoplasma hominis from the CSF of 5 babies undergoing investigation of suspected sepsis or treatment of hydrocephalus. U urealyticum was isolated from 6 infants with severe intraventricular haemorrhage and from 3 with hydrocephalus. In 4 babies multiple isolations were made over several weeks. There were clinical features of congenital infection with major neurological impairment in 1 infant infected with M hominis. Diagnosis is difficult because these organisms cannot be seen on gram stain and cannot readily be cultivated on routine bacteriological media, and CSF pleocytosis may be absent. This study, which used appropriate mycoplasmal media, shows that U urealyticum and M hominis are the most common microorganisms isolated from the CSF of newborn infants in a high-risk population.

Anti-Bacterial Agents↗