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Biomedical subjects

L Cummings

Publications and source records attributed to L Cummings.

14 recordsLinked to original sources

Nonoperative management of spontaneous splenic rupture in infectious mononucleosis: the role for emerging diagnostic and treatment modalities.

Infectious mononucleosis (IM) is a self-limiting lymphoproliferative disorder affecting teenagers and young adults. Splenomegaly is a common manifestation of IM and results in a compromised organ that may rarely rupture spontaneously, with significant morbidity and mortality. The IM spleen should be protected from even minor trauma. Although traditional management of spontaneous splenic rupture in IM has been splenectomy, the role of nonoperative management is evolving. The advent of endovascular interventional modalities has augmented the physician's armamentarium in managing these patients nonoperatively. We report a case of spontaneous splenic rupture in a patient with IM managed conservatively with the aid of splenic angiography. The option of arteriography, with or without embolization, should be considered in the management of all patients with spontaneous splenic rupture in the setting of IM.

Abdominal Pain↗

Pentagon surface wipe sampling health risk assessment.

Within hours after the terrorist attack on the Pentagon on September 11, 2001, an extensive sampling effort was initiated within the building to include surface wipe sampling for select coplanar polychlorinated biphenyls (PCBs), congeners of polychlorinated dibenzo(p)dioxins and dibenzofurans (dioxins/furans) and lead. A risk-based screening level method was utilized to determine the necessity of additional sampling and to assess the potential for emergency response crews, remediation crews, and returning Pentagon workers to have adverse health impact from exposure to the PCBs. dioxins/furans, and lead on nonporous surfaces. The screening level method included all exposure pathways: dermal absorption, incidental ingestion, and inhalation. Various U.S. Environmental Protection Agency (USEPA) guidance documents provided the basis for the method. The underlying assumptions were that the PCBs, dioxins/furans, and lead were contained in the dust or soot layer found on nonporous surfaces, that sampling results were representative of the surfaces from which they were taken, and that the analytical methods employed were able to detect 100% of these substances. A few of the limitations associated with this method included the lack of toxicity values for dermal absorption and the lack of accurate, discrete dermal-exposure values. Evaluation results indicated that additional sampling was not necessary and that concentrations of PCBs, dioxins/furans, and lead on nonporous surfaces were below levels expected to cause adverse health impacts to emergency response crews, remediation crews, and returning Pentagon workers.

Administration, Cutaneous↗

Diurnal variation in the quantitative EEG in healthy adult volunteers.

AIMS: To define the change in power in standard waveband frequencies of quantitative cortical electroencephalogram (EEG) data over a 24 h period, in a drug free representative healthy volunteer population. METHODS: This was an open, non randomised study in which 18 volunteers (9 male and 9 female) were studied on 1 study day, over a 24 h period. Volunteers had a cortical EEG recording taken at 0, 2, 4, 6, 8, 10, 12, 16 and 24 h. Each recording lasted for 6 min (3 min eyes open, 3 min eyes closed). All EEG recordings were taken in a quietened ward environment with the curtains drawn round the bed and the volunteer supine. During the 3 min eyes open, volunteers were asked to look at a red circle on a screen at the foot of the bed, and refrain from talking. RESULTS: Plots produced of geometric mean power by time of the standard wave band frequencies gave some indication of a circadian rhythm over the 24 h period for theta (4. 75-6.75 Hz), alpha1 (7.0-9.5 Hz) and beta1 (12.75-18.50 Hz) wavebands. Mixed models were fitted to both the eyes open and eyes closed data which confirmed a change in mean waveband power with time with statistical significance at the conventional 5% level (P < 0.05). CONCLUSIONS: These data indicate the presence of a diurnal variation in the cortical quantitative EEG. They support the use of a placebo control group when designing clinical trials which utilize quantitative EEG to screen for central nervous system (CNS) activity of pharmaceutical agents, to control for the confounding variable of time of day at which the EEG recordings were made.

Adult↗

Effects of zolmitriptan (Zomig) on central serotonergic neurotransmission as assessed by active oddball auditory event-related potentials in volunteers without migraine.

In this randomized, double-blind, three-period crossover trial, 24 healthy volunteers without migraine received zolmitriptan 5 mg, dexfenfluramine 15 mg or placebo orally. At 2, 6, and 24 h postdose, auditory stimuli of 1000 Hz (nontarget tone) and 2000 Hz (target tone) were randomly and binaurally presented in an active oddball paradigm (4:1 ratio). Cortical auditory evoked responses were recorded for 500 msec poststimulus. Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints. Relative to placebo, zolmitriptan reduced the maximum absolute amplitude, amplitude difference (from nontarget tone noise) and area under the curve of the cortical auditory target tone event-related potential (P300 ERP). The most dramatic effect of zolmitriptan was to diminish the point estimate of noise during the 200-400 msec poststimulus epoch. The effect of zolmitriptan appeared concentration dependent. The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG. Modification by zolmitriptan of the cortical electrical activity evoked by auditory stimuli confirms a central action of this drug in humans, which appears to affect cortical information processing without global alteration of the quantitative EEG.

Acoustic Stimulation↗

Occupational health data as a basis for process engineering changes: development of a safe work environment in the sodium azide industry.

The development of an occupational health system for a plant manufacturing sodium azide has had to confront biological and hygienic difficulties related to the nature of sodium azide. Sodium azide in pellet form is used as the nitrogen generant for automobile air bags; however, it is manufactured as a very fine powder making exposure control more difficult. Sodium azide is a rapidly active, vasodilatory hypotensive agent that causes headaches and drops in blood pressure. Occupational health assessment of the plant and its employees demonstrated the need for exposure control, based on inspection, interviews, health data, process and site review. Targeted studies demonstrated the nature and magnitude of health effect problems at this plant and the relationship to azide exposure. Engineering and hygiene changes were developed in response to the evidence of worker exposure demonstrated by the targeted studies. The occupational health surveillance system provided a monitor for temporal changes. Results appear to demonstrate over the period of the development of the program, the following changes: (1) reductions in evidence of subjective symptoms from azide exposure (health incident reports of headaches and other symptoms), (2) reductions in objective signs of effects from azide exposure (drops in cross-shift mean arterial blood pressures), and (3) reductions in measured levels of azide exposure. Future studies need to validate the evidence of exposure changes and to further identify additional sources of exposure. Interventions designed to reduce exposures need to be demonstrated to be effective and need to be monitored to demonstrate continuing effectiveness.

Azides↗

Overview: medications development for the treatment of drug abuse.

Drug abuse is of great public concern, and effective treatment strategies for opiate and cocaine dependence are urgently needed for the general addict population as well as for pregnant women and their infants. NIDA's effort to develop new pharmacotherapies as an adjunct to the treatment of opiate addiction has already led to the approval of LAAM and an NDA development program for buprenorphine. The momentum achieved by the new Medications Development Program's success with opiate addiction treatment must now be applied to the development of new treatments for cocaine addiction. With recent advances in neuroscience, imaging techniques, and pharmaceutical technology, the development of medications for significantly improving drug abuse treatment in a variety of directions holds real promise.

Cocaine↗

Antisense and sense cDNA expression cloning using autonomously replicating vectors and toxic lectin selection.

CHOP2 cells, a subline of the Chinese hamster ovary (CHO) cell glycosylation mutant Lec2 which expresses polyoma virus large T antigen, was used as the host cell line to select cDNAs conferring resistance to the toxic effects of ricin. Glycoconjugates in CHOP2 cells are deficient in sialic acid and therefore the cells are hypersensitive to ricin, a galactose-binding lectin. CHOP2 cells acquiring cDNA that either corrected the Lec2 mutation or created a Lec2/Lec1 phenotype were expected to show a selective growth advantage in ricin-containing medium. After a single cycle of transfection with a lymphoid cDNA library in pCDM8 followed by ricin selection, the the predominant cDNA recovered from the cells was antisense N-acetyl-glucosaminyltransferase I (GlcNAc-TI) which conferred a Lec2/Lec1 phenotype. cDNA encoding GlcNAc-TI in a sense orientation was also enriched by transfecting a cDNA library into CHOP-1 cells, a mutant deficient in this enzyme, and selecting in medium containing ConA lectin. The results show that cell selection with toxic agents can be used to expression-clone both antisense and sense cDNA sequences from bi-directional cDNA libraries in the pCDM8.

Animals↗

Germ cell deficient (gcd) mouse as a model of premature ovarian failure.

Premature ovarian failure (POF) in women is characterized as menopause commencing before age 35. Although some cases of POF appear to be inherited, no experimental animal models of familial POF are available. Recently a mouse mutation has been identified that results in infertility due to a lack of primordial germ cells arising in early embryonic development. It was observed that shortly after puberty, females homozygous for this mutation entered reproductive senescence as defined by high levels of circulating gonadotropins, inability to respond either hormonally or functionally to superovulation, and a disrupted estrous cycle. Also, the ovaries completely lacked developing follicles and the endometrium was inactive. However, these mice had undergone complete sexual development as determined by age of vaginal opening, mammary gland histology, and sexual behavior. Thus, these animals closely mimic familial premature ovarian failure and may be useful models for study of the pathogenesis and treatment of this condition.

Animals↗

Characterization of synthetic macroporous ion-exchange resins in low-pressure cartridges and columns. Evaluation of the performance of Macro-Prep 50 S resin in the purification of anti-Klenow antibodies from goat serum.

Three ion-exchange materials and one hydrophobic-interaction chromatography packing, based on a rigid macroporous polymer with large, relatively uniform pores, have been evaluated for low-pressure liquid chromatography of antibodies. These sorbents have high capacities for both small and large proteins and are mechanically, chemically, and thermally stable. Macro-Prep 50 S. CM and Q ion-exchange materials are strongly acidic, weakly acidic, and strongly basic, respectively. Protein binding and recovery, pressure-flow properties, and chemical and thermal stability were determined for each sorbent. A rapid, two-step method for the purification of anti-Klenow antibodies from goat serum was developed, based on the Macro-Prep 50 S strong-acid cation-exchange material and the Econo-Pac HIC prepacked hydrophobic-interaction cartridge.

Animals↗

Rapid protein profiling with a novel anion-exchange material.

A new anion-exchange material has been developed which allows very rapid resolution of protein mixtures. The Microanalyzer MA7P matrix consists of small (7 micron), spherical, non-porous, polymethacrylate beads with polyethyleneimine (PEI) covalently coupled to the surface. When packed 30 X 4.6 mm I.D. columns, this matrix is particularly well suited for applications in which 1-300 micrograms of a protein mixture must be resolved in a minimum of time. Recoveries of injected proteins are usually quantitative, even when the amounts of individual proteins are in the submicrogram range. Chromatography on Microanalyzer MA7P columns is characterized by very narrow bandwidths, even at relatively high flow-rates. This is due to the combined effects of short column length, high selectivity, and the lack of velocity-dependent bandbroadening attributable to diffusion into and out of pores. These columns have no discernable gel filtration effects in the molecular weight range from 10(3) to 10(6) daltons. Columns are very rapidly equilibrated with new solvents, further reducing cycle-to-cycle times.

Animals↗

Follow-up of a preschool epidemiological sample: cross-age continuities and predictions of later adjustment with internalizing and externalizing dimensions of behavior.

The continuity of behavioral adjustment from preschool through elementary school and junior high school years was examined. 541 children aged 9-15 years from a preschool epidemiological study were relocated and behavior checklist data obtained. Analyses focused on the relationship between internalizing and externalizing behavior dimensions from the preschool to follow-up periods. It was found that preschool externalizing symptoms were positively correlated with later externalizing and internalizing symptoms in the entire sample. Preschool internalizing symptoms, however, were predictive of later internalizing symptoms only for 2-year-old girls and 5- and 6-year-old boys. Similar results were obtained for clinically disturbed preschoolers. Results are consistent with previous findings regarding the longitudinal continuity of externalizing behavior but are at odds with reports of equal or greater stability of internalizing behavior. Given the magnitude of obtained correlations, even when significant, the results support the view that discontinuity rather than continuity in behavioral adjustment from preschool to later ages is the rule. The importance of examining other mediating variables in the prediction of behavioral adjustment and the need for models of development that encompass both stability and change are discussed.

Adolescent↗

Response of lymphoid leukemia L1210 in mice to implantable sustained release cytosine arabinoside capsules.

The lifespan of BDF mice with ascitic L1210 leukemia is more than doubled when they are treated with a single subcutaneously or intraperitoneally implanted sustained release cytosine arabinoside capsule. These capsules are drug-polymer composites, with dimensions of 1.0 cm in diameter and 0.15 cm in thickness, and a drug content of 17 +/- 3 mg each. Blank silicone rubber discs implanted intraperitoneally or subcutaneously in the leukemic mice produced no beneficial effects. Control healthy mice receiving the ARA-C releasing capsules continued to live with no obvious signs of drug toxicity. In vitro release of ARA-C from the discs was measured. Drug release was maintained above 20 micrograms per day for more than 35 days. ARA-C extracted from discs recovered from implant studies showed that less than 16% of the total drug content was released in vivo.

Animals↗

Response of intramuscular Walker 256 rat tumor to sustained-release cyclophosphamide and ARA-C capsules.

Randomly bred Sprague-Dawley rats with the intramuscular form of Walker 256 tumor growing in the right thigh region were treated with sustained-release cyclophosphamide capsules as well as with cytosine arabinoside capsules. A disk-shaped caps-le was implanted subcutaneously adjacent to the tumor mass. Tumor regression, weight gain, and prolongation of lifespan were observed in animals treated with cyclophosphamide capsules of 10 mg or 20 mg total drug content each. However, the walker 256 intramuscular tumor did not respond to ARA-C capsules implanted, and the animals died at the same rate as the controls, with large ulcerated tumor masses and some metastasis. The in vitro diffusion data of ARA-C capsules is shown. Gross and histological changes associated with cyclophosphamide administered in this manner are reported.

Animals↗

Rapid screening of cervical smears as a method of internal quality control. For how long should we rescreen?

OBJECTIVE: To compare the effectiveness of rapid screening of cervical smears as a method of internal quality control with 10% random rescreening. STUDY DESIGN: From June 5 to July 14, 1995 (6 weeks), all consecutive cervical smears received in the department (n = 8,800) were entered into the study and were prescreened for a duration of 30 seconds (n = 2,938), 1 minute (n = 2,925) or 2 minutes (n = 2,937) over a period of 2 weeks each. RESULTS: Rapid screening of all negative and unsatisfactory smears detected more cytologic abnormalities than would be expected with 10% random rescreening. Thirty-second rapid screening of all negative and unsatisfactory smears was more efficient in detecting false negatives than screening a proportion of the smears for longer periods of time. Rapid screening was also a very effective method of detecting severe cytologic abnormalities in unscreened smears, detecting over 90% of high grade lesions. CONCLUSION: Rapid rescreening of negative and unsatisfactory cervical smears is recommended as a very effective method of internal quality control. It is superior to 10% random rescreening in reducing the false negative rate. Thirty-second rapid rescreening is the most efficient period for which smears should be screened. Rapid screening of unscreened smears could be used as a means of selecting patients for prompt referral when a laboratory backlog exists.

False Negative Reactions↗