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C Markham

Publications and source records attributed to C Markham.

15 recordsLinked to original sources
PubMed2006

Physical environment modulates the behavioral responses induced by chemical stimulation of dorsal periaqueductal gray in mice.

In order to investigate the relationship between behaviors elicited by chemical stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid (5 nmol in 0.1 micro l), was infused into the dorsal PAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period following drug infusion, more jumps were made in the chamber than in the MDTB runway but running time and distance traveled were significantly higher in the runway. Animals were subsequently tested using the standard MDTB procedure (anti-predator avoidance, chase and defensive threat/attack). No drug effects on these measures were significant. In a further test in the MDTB apparatus, the pathway of the mouse during peak locomotion response was blocked 3 times by the predator stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety percent of D,L-homocysteic treated animals made direct contact with the stimulus (rat), indicating that D,L-homocysteic-induced running is not guided by relevant (here, threat) stimuli. These results indicate that running as opposed to jumping is the primary response in mice injected with D,L-homocysteic into the dorsal PAG when the environment enables flight. However, the lack of responsivity to the predator during peak locomotion suggests that D,L-homocysteic-stimulation into the dorsal PAG does not induce normal antipredator flight.

Animals↗
PubMed2004

Infralimbic D1 receptor agonist effects on spontaneous novelty exploration and anxiety-like defensive responding in CD-1 mice.

Mesocortical dopamine (DA) terminals in the ventromedial prefrontal cortex (vmPFC) integrate cognitive/emotional processing functions underlying adaptive and appropriate behavioral responding to stressful environmental events. Results from several studies have also shown that stressor-enhanced prefrontal DA activation exerts detrimental effects on cognitive performance. However, questions have arisen as to whether stressor-enhanced vmPFC DA transmission exerts direct control over conditioned or unconditioned responses to threatening events, or whether enhanced prefrontal DA transmission gates cognitive processing to facilitate adaptive responding in threatening situations. We have previously shown that infralimbic (IL) vmPFC dopamine D2 agonist and antagonist drug infusions reduced anxiety-like responding in the elevated plus-maze (EPM) and disrupted spontaneous exploration in the Y-maze in CD-1 mice. In the present study, the effects of IL vmPFC infusions of the specific D1 receptor agonist, SKF-81297, in CD-1 mice were evaluated on spontaneous exploration in the Y-maze, anxiety-like responding in a 2-trial elevated plus-maze procedure, and anti-predator defensive responding in the Mouse Defense Test Battery (MDTB). SKF-81297 infusions disrupted spontaneous alternation performance along with potentiated repetitive 2-arm responding in the Y-maze. In the elevated plus-maze, pre-trial 1 IL SKF-81297 infusions reduced anxiety-like responding (enhanced open arm entries and time ratio, unprotected stretch attends and head dips), and reduced closed arm time ratio and protected risk assessment activity (protected stretch attends). In trial 2, 24h later (no drug infusions), open arm entries, open time ratio, and unprotected head dips remained enhanced relative to trial 2 vehicle controls. In the MDTB, avoidance distance was enhanced in the approach test; risk assessment (approach) was enhanced in the closed alley test; and defensive threat (upright postures) was enhanced in the forced contact test. Results are discussed with respect to possible influences of IL vmPFC DA receptors on cognitively mediated responding to differing levels of threat in mice.

Aggression↗
PubMed2004

Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior.

The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic-pituitary-adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS + NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS + NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.

Analysis of Variance↗
PubMed2003

A phase II irinotecan-cisplatin combination in advanced pancreatic cancer.

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS>70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity.

Adenocarcinoma↗
PubMed2001

Sexual and aggressive interactions in a visible burrow system with provisioned burrows.

The visible burrow system (VBS) is a habitat providing burrows and an open area for mixed-set rat colonies. Provisioning of food and water in the burrows makes it unnecessary for potentially defensive animals to leave the burrows to eat/drink on the surface, and enables evaluation of new types of agonistic interactions that may emerge when this necessity is removed. In such colonies, subordinate males showed high magnitude tunnel guarding behavior, occupying a tunnel opening onto the surface and confronting the dominant. Dominants, in response, made lunges into the tunnels, but quickly retreated without gaining entry, apparently stopped by contact with the defender's vibrissae. Dominants also made and continued to make lateral attacks to the wall adjacent to the tunnels guarded by subordinates, although these were useless in terms of affording contact with the subordinate. Dominant-female agonistic interactions were more frequent than those of dominants and subordinates. These were largely initiated by the male, and involved female defensive behavior. Nonetheless, females, unlike subordinates, failed to show tunnel guarding and continued to utilize the surface freely. They also spent more time in the vicinity of the dominant over days of colony formation. This apparent paradox may reflect that females were seldom wounded, and that the initial site of male contact with females was the female's anogenital area, findings suggesting that interactions of males and females often reflect male sexual advances, countered by female defenses that effectively protect nonestrus females from mounting and copulation.

Aggression↗
PubMed2000

Cocaine-induced sniffing stereotypy changes in response to threat.

"Cocaine-induced stereotypies" have been extensively investigated on the basis that they may be capable of providing insights into behavioral and neurochemical mechanisms relevant to drug abuse and addiction. Recent work has indicated that cocaine enhances a number of defensive behaviors, and, that cocaine-enhanced sniffing may be a functional behavior pattern, potentially related to defense, prompting an investigation of the effects of threat stimuli on cocaine-enhanced sniffing. When behaviors of saline control rats were evaluated in their home cages (HC), or on exposure to a toy cat (TC) or real cat (RC), they showed minimal crouching in the HC; initial crouching declining over 5 days of repetitions to the TC; and continued, high-level crouching to the RC. Cocaine (30 mg/kg, IP) enhanced defensiveness in situations in which it had declined in the TC and RC groups. It also produced high-level sniffing, declining over 5 test days, in the HC; initial low-level sniffing to the TC, increasing over 5 test days; and very low levels of sniffing to the RC. These and previous data contribute to a view that cocaine enhances, but does not directly induce, defensive behaviors. They also indicate that external threat stimuli such as the RC, or initial presentation of the TC suppress sniffing, with sniffing returning as habituation to novel but not intrinsically dangerous stimuli reduces defensiveness. This view suggests that some component of "sensitization of cocaine-induced sniffing stereotypy" may reflect a release from defensiveness-mediated suppression of sniffing over repeated injection/testing as the subject becomes habituated to the injection procedure and to novel test situations.

Animals↗
PubMed2000

Impact of HIV-positive speakers in a multicomponent, school-based HIV/STD prevention program for inner-city adolescents.

Qualitative and quantitative data from Safer Choices, a school-based multicomponent HIV prevention program, were examined to determine the impact of HIV-positive speakers on inner-city adolescents' HIV risk perception and empathy for people with HIV or AIDS. Inductive analyses were used to assess student reactions to speakers. Multilevel regression modeling techniques were used to analyze student survey data (n = 1,491) to determine the effect of speakers alone, as well as in combination with the multicomponent intervention, and a knowledge-based curriculum (comparison condition). Results showed that speakers were highly popular with students and teachers, and had a positive short-term impact on students' attitudes. Although not statistically significant, the combination of intervention and speakers had the greatest impact on outcome variables. Integrating HIV-positive speakers into multicomponent programs may have a positive impact on inner-city youth. Utilizing speakers without other educational components may have minimal effects. Strategies for training and utilizing HIV-positive speakers in school settings are included.

Adolescent↗
PubMed1999

The power of the visible: the meaning of diagnostic tests in chronic back pain.

This article explores the meaning of diagnostic tests for people with chronic back pain. Lower back pain is one of the most common health problems in the US. Five to ten percent of the patients who visit a primary care provider for back pain ultimately develop a chronic condition. We draw on interviews with chronic back pain patients in Atlanta, Dallas and Seattle to argue that testing constitutes an important element in the legitimation of pain for these patients. We discuss three aspects that make testing an area of concern for patients: a strong historical connection between visual images and the medicalization of the interior of the body, a set of cultural assumptions that make seeing into the body central to confirming and normalizing patients' symptoms, and the concreteness of diagnostic images themselves. Our interviews show that when physicians cannot locate the problem or express doubt about the possibility of a solution, patients feel that their pain is disconfirmed. Faced with the disjunction between the cultural model of the visible body and the private experience of pain, patients are alienated not only from individual physicians but from an important aspect of the symbolic world of medicine. This paper concludes by suggesting that a fluid, less localized understanding of pain could provide a greater sense of legitimacy for back pain patients.

Adult↗
PubMed1998

Reasons for repeated medical visits among patients with chronic back pain.

OBJECTIVE: This study identifies the key motivations of patients repeatedly seeking medical care for chronic back problems. DESIGN: We conducted one-on-one, in-depth interviews with patients to discuss their experiences with low back pain and its care. To validate our interpretation of the qualitative data, participants were mailed questionnaires listing the themes identified in the interviews and asked to rate the importance to them of each of the themes. SETTING: Managed health care plans in Atlanta, Dallas, and Seattle. PARTICIPANTS: Fifty-four patients (37% male, 63% female) who were 25 to 65 years of age and had three or more medically attended episodes of low back pain during the 3 years preceding the study. MAIN RESULTS: In describing their motivations for seeking medical care for back pain, nearly all participants cited difficulty in performing normal activities and the desire to discover the cause of the pain. Other motivations for seeking medical care for back pain included increased pain and the desire for a diagnostic test or a new treatment. Many of the verbalized reasons for repeated medical visits among patients with chronic back pain are probably best understood as seeking validation of their suffering. CONCLUSIONS: Patients with chronic back pain report many unmet needs and expectations. Overall satisfaction might be improved if clinicians elicit patients' views of underlying causes and their expectations from office visits.

Activities of Daily Living↗
PubMed1994

Hereditary variations in monoamine oxidase as a risk factor for Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies suggest that several genes may have a role in determining individual susceptibility to this disease, and the degradative enzyme monoamine oxidase (MAO) has been implicated in the disease process. Wide differences in activity levels for both forms of this enzyme (MAO-A and MAO-B) exist in the human population, and levels of both are genetically determined. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci on the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length polymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n repeat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was significantly different (p = 0.03) between these two groups. Another MAOA haplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0.046). These findings support the idea that the MAO genes may be among the hereditary factors that influence susceptibility of individuals to PD.

Adolescent↗
PubMed1980

Pyrogastrone treatment of peptic oesophagitis: analysis of 104 patients treated during a 3 1/2-year period.

A retrospective analysis was carried out in 104 patients with peptic oesophagitis treated with Pyrogastrone (carbenoxolone with alginate-antacid) during a 3 1/2-year period. There wer 3 treatment groups: one had Pyrogastrone alone, another pyrogastrone with metoclopramide and in the third, both agents were given together with cimetidine. Highly significant symptomatic improvement was achieved in 85% of 96 patients treated between 4 and 8 weeks and equally significant endoscopic healing was noted in 76% of 55 patients for the same period. Best results were seen in those given Pyrogastrone alone; the concurrent use of metoclopramide and cimetidine did not enhance healing or symptom relief. 40% of patients received multiple courses, 22% were treated for at least six months and 16% for one year or longer continuously; 3 patients for over 3 years. The only noteworthy side effects were due to the tablet flavour and chewing property. These results confirm clinical trial experience that Pyrogastrone is highly effective in healing peptic esophagitis.

Adult↗