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Biomedical subjects

C M Anderson

Publications and source records attributed to C M Anderson.

At least 73 records · Page 4Linked to original sources

Reaching targets in the national cervical screening programme: are current practices unethical?

The principle of informed consent is now well established within the National Health Service (NHS) in relation to any type of medical treatment. However, this ethical principle appears to be far less well established in relation to medical screening programmes such as Britain's national cervical screening programme. This article will critically examine the case for health care providers vigorously pursuing women to accept an invitation to be screened. It will discuss the type of information which women would need in order to make an informed decision about whether or not to be screened. The lack of such information in current patient leaflets on the "smear test" will then be documented. Finally, the article will explore possible ways of maximising women's autonomy in relation to the cervical screening programme without sacrificing any of its main benefits.

Adult↗

Perception of foreign cigarettes and their advertising in China: a study of college students from 12 universities.

OBJECTIVE: To examine how deeply foreign cigarette advertising had penetrated the Chinese market when a new ban on cigarette advertising was enacted in February 1995. DESIGN: A survey using self-completion questionnaires administered in college classrooms from November 1994 to March 1995. SETTINGS: Eight universities and four medical schools in three Chinese cities: Beijing, Wenzhou, and Hangzhou. SUBJECTS: 1896 college students who agreed to complete a written questionnaire. The mean age was 21.2 years; 39.5% of respondents were female. RESULTS: Four of the top eight cigarette brands most familiar to the respondents were foreign: Marlboro, 555, Kent, and Hilton. Advertisements for the foreign brands were much more likely to be seen than those for the domestic brands; those for Marlboro were reported most often (29.7%), followed by 555 (21.8%) and Kent (18.1%). Among smokers, Marlboro was the most preferred foreign brand, by 44.2%. The preference for Marlboro was also correlated with smokers having seen its advertisements. Most respondents, 71.8%, believed that cigarette advertising should be banned. CONCLUSIONS: The previous restrictions on cigarette advertising in China failed to prevent a large portion of the population from seeing and understanding the advertisements. Before the 1995 advertising ban took effect, strict limitations on imports of foreign cigarettes notwithstanding, certain highly advertised brands such as Marlboro achieved wide recognition and even consumer preference. Stricter restrictions are suggested as previous ones have failed to achieve their intended effects.

Adolescent↗

Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities.

The activity of the AF-2 transcriptional activation function of nuclear receptors (NR) is mediated by the partially homologous transcriptional coactivators, glucocorticoid receptor interacting protein 1 (GRIP1)/transcriptional intermediary factor 2 (TIF2) and steroid receptor coactivator 1 (SRC-1). GRIP1 and SRC-1 bound nine different NRs and exhibited similar, but not identical, NR binding preferences. The most striking difference was seen with the androgen receptor, which bound well to GRIP1 but poorly to SRC-1. GRIP1 and SRC-1 contain three copies of the NR binding motif LXXLL (called an NR Box) in their central regions. Mutation of both NR Box II and NR Box III in GRIP1 almost completely eliminated functional and binding interactions with NRs, indicating that these two sites are crucial for most of GRIP1's NR binding activity. Interactions of GRIP1 with the estrogen receptor were more strongly affected by mutations in NR Box II, whereas interactions with the androgen receptor and glucocorticoid receptor were more strongly affected by NR Box III mutations. One isoform of SRC-1 has an additional NR Box (NR Box IV) at its extreme C terminus with an NR-binding preference somewhat different from that of the central NR-binding domain of SRC-1. GRIP1 has no NR Box in its C-terminal region and therefore no C-terminal NR-binding function. In summary, GRIP1 and SRC-1 have overlapping NR-binding preferences, but specific NRs display both coactivator and NR Box preferences that may contribute to the specificity of hormonal responses.

Amino Acid Sequence↗

Why functional assessment is enough: a response to Reiss and Havercamp.

Reiss and Havercamp (1997) recently suggested that sensitivity theory offers a basis from which to assess and treat challenging behavior exhibited by people with developmental disabilities. They contended that this approach would lead to more effective and durable interventions than would reliance on functional assessment. We respond to their claim that functional assessment is "not enough." After briefly reviewing and critiquing sensitivity theory, we outline the basic tenets of behavior analysis and describe literature on the development and use of functional assessment methodologies with individuals with developmental disabilities exhibiting challenging behavior, responding to several of Reiss and Havercamp's comments about the utility of this approach. Finally, we discuss several limitations of behavior analysis and functional assessment, providing examples of how these limitations are being addressed.

Activities of Daily Living↗

Coincident renal cell carcinoma and nonHodgkin's lymphoma: the M. D. Anderson experience and review of the literature.

PURPOSE: We recently observed nonHodgkin's lymphoma and renal cell carcinoma occurring simultaneously in several patients. We determine whether the incidence of co-occurrence of the 2 malignancies is greater than expected based on the incidence of each disease in the general population. MATERIALS AND METHODS: Patients diagnosed with simultaneous renal cell carcinoma and nonHodgkin's lymphoma were identified through the medical informatics data base at our cancer center. Charts of all patients were reviewed to collect detailed demographic information and confirm both diagnoses. United States population based cancer statistics (Surveillance, Epidemiology and End Results Program data) were used to arrive at the expected age adjusted incidence of co-occurrence of these diagnoses, and statistical analysis was performed to ascertain any differences between expected and observed incidences. RESULTS: We identified 41 cases with both diagnoses between 1954 and 1995, including 21 diagnosed after 1987. The latter group was used for statistical analysis. The observed rates of renal cell carcinoma developing in the nonHodgkin's lymphoma population (1.86) and nonHodgkin's lymphoma developing in the renal cell carcinoma population (2.67) were greater than expected and both reached statistical significance. CONCLUSIONS: There is a higher than expected incidence of co-occurrence of renal cell carcinoma and nonHodgkin's lymphoma. The cause remains speculative.

Carcinoma, Renal Cell↗

Morphology and membrane properties of neurones in the cat ventrobasal thalamus in vitro.

1. The morphological (n = 66) and electrophysiological (n = 41) properties of eighty-six thalamocortical (TC) neurones and those of one interneurone in the cat ventrobasal (VB) thalamus were examined using an in vitro slice preparation. The resting membrane potential for thirty-seven TC neurones was -61.9 +/- 0.7 mV, with thirteen neurones exhibiting delta oscillation with and without DC injection. 2. The voltage-current relationships of TC neurones were highly non-linear, with a mean peak input resistance of 254.4 M omega and a mean steady-state input resistance of 80.6 M omega between -60 and -75 mV. At potentials more positive than -60 mV, outward rectification led to a mean steady-state input resistance of 13.3 M omega. At potentials more negative than -75 mV, there was inward rectification, consisting of a fast component leading to a mean peak input resistance of 14.5 M omega, and a slow time-dependent component leading to a mean steady-state input resistance of 10.6 M omega. 3. Above -60 mV, three types of firing were exhibited by TC neurones. The first was an accelerating pattern associated with little spike broadening and a late component in the spike after-hyperpolarization. The second was an accommodating or intermittent pattern associated with spike broadening, while the third was a burst-suppressed pattern of firing also associated with spike broadening, but with broader spikes of a smaller amplitude. All TC neurones evoked high frequency (310-520 Hz) burst firing mediated by a low threshold Ca2+ potential. 4. Morphologically TC neurones were divided into two groups: Type I (n = 31 neurones) which had larger soma, dendritic arbors that occupied more space, thicker primary dendrites and daughter dendrites that followed a more direct course than Type II (n = 35). The only electrophysiological differences were that Type I neurones (n = 16) had smaller peak input and outward rectification resistance and spike after-hyperpolarization, but greater peak inward rectification resistance, and exhibited delta oscillation less often than Type II (n = 13). 5. The morphologically identified interneurone exhibited no outward rectification, only moderate inward rectification, and no high frequency firing associated with the offset of negative current steps below -55 mV. This interneurone had a regular accommodating firing pattern, but the spike after-hyperpolarization had a late component, unlike the accommodating firing in TC neurones. 6. Therefore, the differentiation of TC neuronal types in the cat VB thalamus based on their morphology was reflected by differences in peak input resistance, outward rectification and spike after-hyperpolarization, which could be accounted for by their difference in soma size. More importantly, the firing pattern of the majority of TC neurones in the cat VB thalamus were different from those of TC neurones in other sensory thalamic nuclei. 7. Thalamocortical neurones in the cat VB thalamus were also clearly distinguishable from the interneurone based on the presence of their prominent outward rectification, peak inward rectification and robust low threshold Ca2+ potentials.

Action Potentials↗

Potential signalling roles for UTP and UDP: sources, regulation and release of uracil nucleotides.

Increasing evidence for receptors for uracil nucleotides has focused interest on specific signalling mechanisms involving UTP and UDP. At least three metabotropic P2 receptors are stimulated by uracil nucleotides with equal or greater potency than by adenine nucleotides, and there might be ionotropic receptors as well. Regulation of uridine and uracil nucleotide levels is important when considering the receptor-mediated effects of these compounds. Cells can synthesize uracil nucleotides de novo or by salvage of uridine. UTP made from salvage might be preferentially used for RNA synthesis in the nucleus, while UTP synthesized de novo seems to be used for UDP-sugar and CDP-phospholipid production. UTP from both pathways can enter a free UTP pool, from which UTP can be released from cells. UTP and UDP can stimulate pyrimidinoceptors, but metabolism by ecto-nucleotidases limits their effects. Alternatively, UTP might be a substrate for ecto-protein kinases, and this could contribute to its extracellular regulation. Cells can reclaim uridine, using nucleoside transport processes, following dephosphorylation of UTP, UDP and UMP. In this article Christopher Anderson and Fiona Parkinson discuss how understanding the processes that regulate uridine and uracil nucleotide concentrations will enhance our ability to manipulate UTP/UDP signalling pathways for pharmacological effect.

Animals↗

Transcriptional activities of estrogen and glucocorticoid receptors are functionally integrated at the AP-1 response element.

Estrogens and glucocorticoids often act in opposition to regulate physiological responses. We investigated whether this might reflect the opposing actions of hormone-bound receptors on target genes regulated by the AP-1 response element. We performed a series of transfection experiments in which transcriptional activation, mediated by the AP-1 response element, was reflected in reporter gene activity. As previously described, we found that estrogens stimulate, whereas the glucocorticoid dexamethasone (Dex) inhibits, transcription through a model promoter from the collagenase gene (-73 to +63). This promoter bears a consensus AP-1 response element. When HeLa cells were treated with both estradiol and Dex, the steroids counteracted each other's transcriptional effects. The amount of transfected estrogen and glucocorticoid receptors (ER and GR) determined the extent to which Dex blunted estrogen stimulation or estrogen prevented Dex inhibition. The ER/GR interaction was observed both in the presence of estradiol and tamoxifen, which has previously been shown to have estrogen-like action at an AP-1 response element. The AP-1 family member c-Jun enhanced Dex inhibition and estradiol stimulation of transcriptional activation. c-Fos potentiated the effect of cotransfected c-Jun on estradiol stimulation but not Dex inhibition. The pattern of steroid responses was retained in the presence of the c-Jun activator phorbol 12-myristate 13-acetate. However, estradiol stimulation was lost in the presence of the c-Jun activator tumor necrosis factor-alpha. The ER/GR/AP-1 response element interaction was present, not only in a cell line originally derived from a uterine cervical adenocarcinoma (HeLa), but also in a cell line derived from the hypothalamus (GT1-1). Lastly, both progesterone receptor types A and B also interacted with the ER at the AP-1 site. These data indicate that opposing steroid influences can be mediated at the level of transcription through the AP-1 site and suggest that the integration of hormone action at this response element may underlie some of the opposing actions of estrogens and glucocorticoids or progestins on physiological responses.

Dexamethasone↗

Ability of nitrobenzylthioinosine to cross the blood-brain barrier in rats.

Nucleoside transport inhibitors that cross the blood-brain barrier may be able to potentiate the neuroprotective effects of adenosine. We tested whether nitrobenzylthioinosine (NBMPR) crosses the blood-brain barrier in three types of experiments. First, intravenous injection of [3H]NBMPR and [14C]sucrose was performed. Brain volume of distribution and brain delivery were greater for [3H]NBMPR than for [14C]sucrose. Second, rats were injected intraperitoneally with NBMPR 5'-monophosphate (NBMPR-P), a prodrug form of NBMPR, or vehicle. Perchloric acid extracts of brains from rats treated with NBMPR-P inhibited [3H]NBMPR binding in competition binding assays nearly 3-fold more than extracts from brains of vehicle-treated animals. Third, cerebrospinal fluid (CSF) extracted from rats treated with NBMPR-P (10 mg/kg i.p.) contained 24.1 +/- 4.4 nM NBMPR while levels were undetectable in CSF from vehicle-treated rats. From these data, we conclude that NBMPR crosses the blood-brain barrier.

Animals↗

The postwar hospitalization experience of U.S. veterans of the Persian Gulf War.

BACKGROUND: Since the Persian Gulf War ended in 1991, many veterans of that conflict have reported diverse, unexplained symptoms. To evaluate the health of Gulf War veterans, we studied their postwar hospitalization experience and compared it with that of other military personnel serving at the same time who did not go to the Persian Gulf. METHODS: Using a retrospective cohort approach and data from Department of Defense hospitals, we studied hospitalizations of 547,076 veterans of the Gulf War who were serving in the Army, Navy, Marine Corps, and Air Force and 618,335 other veterans from the same era who did not serve in the Persian Gulf. Using multivariate logistic-regression models, we analyzed risk factors for hospitalization both overall and in 14 broad diagnostic categories during three periods from August 1991 through September 1993 (a total of 45 specific comparisons). RESULTS: After the war, the overall odds ratio for hospitalization of the Gulf War veterans was not higher than that of the other veterans, even after adjustment for selection effects related to deployment. In 16 of the 42 comparisons involving specific diagnoses, the risk of hospitalization among Gulf War veterans differed significantly from that among other veterans. Among these 16 comparisons, Gulf War veterans were at higher risk in 5: neoplasms (largely benign) during 1991, diseases of the genitourinary system during 1991, diseases of the blood and blood-forming organs (mostly forms of anemia) during 1992, and mental disorders during both 1992 and 1993. The differences were not consistent over time and could be accounted for by deferred care, postwar pregnancies, and postwar stress. CONCLUSIONS: During the two years after the Persian Gulf War, there was no excess of unexplained hospitalization among Americans who remained on active duty after serving in that conflict.

Adult↗

Electrophysiological and morphological properties of interneurones in the rat dorsal lateral geniculate nucleus in vitro.

1. Intracellular recordings were made from putative interneurones (n = 24) and thalamocortical (TC) projection neurones (n = 45) in slice preparations of the rat dorsal lateral geniculate nucleus (dLGN) in order to compare the electrophysiological properties of these neuronal types. 2. Intracellular injection of biocytin to electrophysiologically identified neurones (n = 34) revealed the morphology of putative interneurones (n = 4) to be similar to class B and that of TC neurones (n = 30) to be similar to class A Golgi-impregnated neurones. 3. Interneurones had resting membrane potentials (-52 mV) relatively positive to those of TC neurones (-63 mV), shorter time constants (36.8 and 58.2 ms, respectively), but similar steady-state input resistances (164 and 180 M omega, respectively). Steady-state voltage-current relationships were nearly linear in interneurones, but highly non-linear in TC neurones. 4. The structure of action potential firing evoked at the break of hyperpolarizing voltage transients was dependent upon neuronal type. Interneurones fired a single action potential or a burst of action potentials with a maximum frequency of < 130 Hz, whilst TC neurones fired a high frequency burst with a minimum frequency of > 250 Hz. In addition, well-defined burst firing of action potentials in response to depolarizing voltage excursions, from membrane potentials negative to -65 mV, could be evoked in TC neurones, but not in interneurones. 5. The directly evoked action potentials of interneurones were characterized by an initial slow pre-potential preceding the fast upstroke of the action potential. The amplitude and width of interneurones' action potentials were smaller than those of TC neurones and the amplitude and duration of the single action potential after-hyperpolarization were greater in interneurones. Both interneurones and TC neurones fired action potentials repetitively in response to suprathreshold voltage excursions, with interneurones demonstrating a greater degree of spike-frequency adaptation. Following a train of action potentials, interneurones and TC neurones generated a slow after-hyperpolarizing potential: in interneurones but not TC neurones this potential was followed by a slow depolarizing potential. 6. An intrinsic, subthreshold membrane potential oscillatory activity with a mean frequency of approximately 8 Hz was observed in interneurones. 7. Electrical stimulation of the optic tract evoked in interneurones apparently pure EPSPs, pure IPSPs or a mixture of EPSPs and IPSPs. EPSPs were found to be biphasic and mediated by the activation of non-N-methyl-D-aspartate (NMDA) and NMDA excitatory amino acid receptors. IPSPs and the response to the iontophoretic application of GABA were found to reverse between -65 and -70 mV. The application of GABAB receptor agonists failed to affect the membrane properties of six of seven interneurones tested. In addition spontaneous EPSPs and IPSPs were recorded in interneurones. 8. These results demonstrate that the electrophysiological properties of putative interneurones are distinct from those of TC neurones of the rat dLGN. The implications of these findings for the control of visual responsiveness of TC neurones are discussed.

Animals↗

Demonstration of the existence of mRNAs encoding N1/cif and N2/cit sodium/nucleoside cotransporters in rat brain.

Nucleoside transport may be involved in the regulation of extracellular levels of adenosine, an inhibitory neuromodulator in the central nervous system. Previous reports have provided functional evidence for Na+-dependent nucleoside transport in rat brain. We isolated total RNA from various regions of rat brain and tested for the presence of mRNA for two recently cloned Na+/nucleoside cotransporters using reverse transcriptase PCR (RT-PCR). Messenger RNA for a pyrimidine-selective Na+/nucleoside cotransporter mRNA (rCNT1) was detected in samples from each brain region tested by RT-PCR amplification of a 309-bp DNA product. Southern blot and sequence analysis confirmed that this product was derived from rCNT1 mRNA. A purine-selective Na+/nucleoside cotransporter mRNA (rCNT2, also termed SPNT) was detected throughout brain by amplifying a 235-bp DNA product, the sequence of which was identical to that published. These experiments demonstrate the presence of both rCNT1 and rCNT2 mRNA in rat brain.

Animals↗

Mediastinitis related to probable central vinblastine extravasation in a woman undergoing adjuvant chemotherapy for early breast cancer.

Adjuvant chemotherapy for breast cancer, although generally safe and of proven benefit, can have severe complications. Central venous catheter (CVC) complications are relatively common forms of treatment-related morbidity in this setting. We report a rare type of CVC-related complication, that of chemotherapy-induced mediastinitis from central venous extravasation of the drug vinblastine, in a women undergoing adjuvant chemotherapy. The patient presented with signs and symptoms consistent with mediastinitis, but the diagnosis was delayed because the initial findings were nonspecific and there was little suspicion for a CVC-related problem. A radionuclide venous flow study was misleading, but a computed tomographic study of the chest and contrast venography confirmed the diagnosis. Conservative treatment with CVC removal, systemic anticoagulation, antibiotics, and pain controlled to gradual improvement in the patient's clinical status. More aggressive strategies, such as thrombolytic therapy and surgical intervention, were considered, but these approaches have not been used in this particular setting. The complication reported here is the first described in the literature in an adult patient. Two similar cases have been reported in pediatric patients. It is likely that this clinical problem is underreported. Patients with CVCs actively undergoing chemotherapy with vesicant agents should be watched carefully for early signs of CVC disruption and subsequent extravasation, as it is likely that early intervention will be of benefit.

Amoxicillin↗

Coronal plane rotation of the first metatarsal.

A method for measuring first metatarsal rotation on weightbearing tangential radiographs is described. Under controlled conditions using cadaver specimens, 5 degree changes in first metatarsal rotation were associated with a mean change in radiographically measured rotation of 5.4 degrees (SD = 1.7 degrees). A clinical study of 30 hallux valgus and 30 control patients was undertaken to assess the reliability of the method of measurement. The overall reliability was high for both hallux valgus and control patients (r = 0.93 and 0.95, respectively). In these two groups, no significant difference was found between the mean values for first metatarsal rotation. Likewise, we found no correlation between first metatarsal rotation measured on tangential standing ("sesamoid" view) radiographs and the first metatarsophalangeal angle or the intermetatarsal 1-2 angle measured on anteroposterior standing radiographs.

Analysis of Variance↗