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Biomedical subjects

C R Green

Publications and source records attributed to C R Green.

At least 19 recordsLinked to original sources

Connexin43 gap junction protein plays an essential role in morphogenesis of the embryonic chick face.

Normal outgrowth and fusion of facial primordia during vertebrate development require interaction of diverse tissues and co-ordination of many different signalling pathways. Gap junction channels, made up of subunits consisting of connexin proteins, facilitate communication between cells and are implicated in embryonic development. Here we describe the distribution of connexin43 and connexin32 gap junction proteins in the developing chick face. To test the function of connexin43 protein, we applied antisense oligodeoxynucleotides that specifically reduced levels of connexin43 protein in cells of early chick facial primordia. This resulted in stunting of primordia outgrowth and led to facial defects. Furthermore, cell proliferation in regions of facial primordia that normally express high levels of connexin43 protein was reduced and this was associated with lower levels of Msx-1 expression. Facial defects arise when retinoic acid is applied to the face of chick embryos at later stages. This treatment also resulted in significant reduction in connexin43 protein, while connexin32 protein expression was unaffected. Taken together, these results indicate that connexin43 plays an essential role during early morphogenesis and subsequent outgrowth of the developing chick face.

Animals↗

Detection of submicroscopic magnetite particles using reflectance mode confocal laser scanning microscopy.

Light microscopy and transmission electron microscopy work at such different scales that some components of cells may be too small to detect using light microscopy but too dispersed among cells within tissues to be discovered using electron microscopy. We have used reflectance mode confocal laser scanning microscopy to detect single-domain magnetite crystals in both live and resin-embedded preparations of magnetotactic bacteria. We show that reflections from bacterial cells are uniquely associated with the magnetite, which underpins the magnetotactic response of the bacteria. En bloc viewing shows that relatively large volumes of material can be searched with sufficient resolution to enable detection of submicroscopic particles. The techniques reported here may be of interest to others wishing to detect submicroscopic objects dispersed in large volumes of tissue.

Bacteria↗

Analysis of the physician variable in pain management.

BACKGROUND: The role of physician variability in pain management is unknown. OBJECTIVE: To assess the role of physician variability in the management of pain and provide quantitative data regarding the status of pain management in Michigan. DESIGN: A multi-item mail survey was used to determine the physician's perceived knowledge of pain management modalities, goals, satisfaction, and confidence with pain treatment. Participants. The focus of this report was a group of 368 licensed Michigan physicians who provide clinical care. RESULTS: Overall, 30% of the study group reported no formal education in pain management, although younger physicians reported more education (correlation coefficient = -0.252, P <.001). The physicians reported greater confidence in their knowledge of meperidine than other Schedule II opioids (P <.001 ). In regards to the opinion that prescribing strong opioids would attract a medical review, the physician responses ranged from 1 (strongly disagree) to 5 (strongly agree). The median score for this scale was 4, accounting for 46% of the responses. The study group expressed less satisfaction with their treatment of chronic pain as well as lower goals for relief (mean: 3.8; 95% confidence interval: 3.7-3.9). CONCLUSIONS: Lower expectations for relief and less satisfaction in its management may contribute to the undertreatment of chronic pain. Perceptions of regulatory scrutiny may contribute to suboptimal pain management. These preliminary data highlight physician variability in pain decision making while providing insights into educational needs.

Journal Article↗

The role of childhood and adulthood abuse among women presenting for chronic pain management.

OBJECTIVE: This study investigated the association between repeated childhood and adulthood abuse and somatic symptom reporting, mental health care use, and substance use among women with chronic pain. DESIGN: A survey of a consecutive sample. PATIENTS: Ninety consecutive women patients presenting for chronic pain management at a multidisciplinary pain management center. OUTCOME MEASURES: The authors assessed the presence or absence of physical or sexual abuse (using the Drossman Physical-Sexual Abuse Survey), period of abuse, demographics, mental health care use, drug or alcohol use and substance abuse, and the presence or absence of physical, pain, and anxiety (somatic) symptoms. RESULTS: The response rate among patients surveyed was 64%. Of the 43 respondents (48%) who reported abuse, 17 (40%) cited childhood abuse, 12 (28%) cited adulthood abuse, and 14 (33%) cited repeated abuse. Women describing long-term abuse reported a significantly greater number of physical, pain, and anxiety symptoms and were more likely to report a history of substance abuse than women reporting abuse during childhood or adulthood alone. CONCLUSIONS: These data indicate a significant association between health status and reported abuse among women presenting to a multidisciplinary pain center for pain management. This finding is consistent with those of previous investigators, and emphasizes the importance of routine evaluation of the presence of long-term abuse as a possible predictor of the onset of chronic pain states.

Adult↗

Magnetite defines a vertebrate magnetoreceptor.

The key behavioural, physiological and anatomical components of a magnetite-based magnetic sense have been demonstrated in rainbow trout (Oncorhynchus mykiss). Candidate receptor cells located within a discrete sub-layer of the olfactory lamellae contained iron-rich crystals that were similar in size and shape to magnetite crystals extracted from salmon. Here we show that these crystals, which mapped to individual receptors using confocal and atomic force microscopy, are magnetic, as they are uniquely associated with dipoles detected by magnetic force microscopy. Analysis of their magnetic properties identifies the crystals as single-domain magnetite. In addition, three-dimensional reconstruction of the candidate receptors using confocal and atomic force microscopy imaging confirm that several magnetic crystals are arranged in a chain of about 1 microm within the receptor, and that the receptor is a multi-lobed single cell. These results are consistent with a magnetite-based detection mechanism, as 1-microm chains of single-domain magnetite crystals are highly suitable for the behavioural and physiological responses to magnetic intensity previously reported in the trout.

Animals↗

Tests of a cognitive-resource-allocation account of the bizarreness effect.

The authors examined the role of cognitive-resource allocation in obtaining the often reported memory advantage for bizarre relative to common information by using the secondary-task method in 4 experiments. In Experiments 1 and 2, they investigated the relationship between differences in cognitive resource allocation during comprehension and in recall for common and bizarre information. In Experiments 3 and 4, they investigated the same relationship but measured cognitive-resource allocation during imaging rather than during comprehension. Although bizarre items required more time to comprehend and to image than did common items, the differences were not reliable predictors of the recall differences between item types. Furthermore, analyses of response latencies to a secondary task provided no compelling evidence in support of a cognitive-resource-allocation explanation of bizarreness effects. Implications for the development of a comprehensive model of the influence of bizarreness on memory are discussed.

Adult↗

Use of the McGill Pain Questionnaire to compare women with vulvar pain, pelvic pain and headaches.

OBJECTIVE: To assess differences between women with three distinct types of chronic pain conditions using a modified McGill Pain Questionnaire. STUDY DESIGN: Data by self-administered questionnaire were collected on patients presenting to the University of Michigan Medical Center with chronic vulvar pain (144 patients), pelvic pain (198 patients) or headaches (130 patients). Data for analysis included: patient demographics, duration of pain and modified McGill Pain Questionnaire scores. Univariate and multivariate analyses were performed. RESULTS: Patients with vulvar pain had more formal education (P < .001), were more likely to be married (P < .001) and were less likely to be African American (P = .003) as compared to those with chronic pelvic pain and headaches. Chronic pelvic pain patients were younger than those in the other two groups (P = .002), and headache patients were likely to have had their chronic pain for a shorter duration than those with vulvar or pelvic pain (P < .001). Patients with vulvar pain had lower total scores on the McGill Pain Questionnaire as well as on the four subsets of variables: affective, sensory, cognitive and miscellaneous indexes (P < .001). They also chose fewer words to describe their symptoms from the 20-word lists (P < .001) and had lower average scores in each of the 20 categories as compared to the other two groups (P < .0001). Controlling for age, ethnicity and marital status did not alter this significance. CONCLUSION: Patients with vulvar pain were a unique groups when compared to other chronic pain populations. Evaluation of the demographics and McGill Pain Questionnaire scores confirmed the distinct qualities of women with vulvar pain.

Age Factors↗

The impact of behavioral impairment of functional ability in Alzheimer's disease.

This study sought to determine the relationship between behavioral disturbance and functional status in a longitudinally studied sample of patients with Alzheimer's disease (AD). One hundred and forty-nine patients meeting NINCDS-ADRDA criteria for probable AD were followed for an average of 37.3 months, with follow-up assessments every 6 months. Subjects were seen at the Alzheimer's Disease Research Center clinics at the Mt Sinai Medical Center, New York, and the Veterans Affairs Medical Center, Bronx, New York. Measures included the Physical and Self-Maintenance Scale (PSMS) and Instrumental Activities of Daily Living Scale (IADLS) of Lawton and Brody and the cognitive and non-cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS). For each patient the assessment at which they had their most severe non-cognitive symptoms as measured by the non-cognitive part of the ADAS (ADAS-NC) was determined. ADAS-NC scores at that assessment were correlated with IADLS and PSMS scores at the same assessment and at the next assessment 6 months later. While there was some modest association of ADAS-NC scores with functional impairment using pairwise correlation coefficients, none of the correlations remained significant when the severity of cognitive impairment was controlled statistically. Findings were not significantly changed when drug status was controlled. These results suggest that behavioral disturbance, while very troubling to caregivers and patients, does not substantially worsen functional ability beyond the contribution of cognitive impairment in AD. Together with previous results indicating that non-cognitive symptoms in AD are episodic and fluctuating rather than progressive, the present data suggest that interventions for non-cognitive disturbances in AD should be viewed as ways to increase patient comfort, safety and ease of care and not as ways to improve functional autonomy. The latter can be achieved only by improving the progressive cognitive deficits of AD.

Activities of Daily Living↗

Roles for alpha 1 connexin in morphogenesis of chick embryos revealed using a novel antisense approach.

Gap junctional communication has been implicated in embryonic development and pattern formation. The gap junction protein, alpha 1 connexin (Cx43) is expressed in dynamic and spatially restricted patterns in the developing chick embryo and its expression correlates with many specific developmental events. High levels of expression are found in regions of budding, which leads to shaping and appears to be a necessary prelude for tissue fusions. In order to investigate the role of alpha 1 connexin in these morphogenetic events, we developed a novel method of applying unmodified antisense deoxyoligonucleotides (ODNs) to chick embryos. The use of pluronic gel to deliver antisense ODNs has allowed us to regulate the expression of alpha 1 connexin protein, both spatially and temporally. This "knockdown" results in some striking developmental defects that mimic some common congenital abnormalities, such as spina bifida, anencephaly, myeloschisis, limb malformation, cleft palate, failure of hematopoiesis, and cardiovascular deformity. The results imply a major role for alpha 1 connexin communication in the integration of signaling required for pattern formation during embryonic development. This novel antisense technique may also be widely applicable.

Animals↗

Do physical and sexual abuse differentially affect chronic pain states in women?

To evaluate the role of physical and/or sexual abuse on chronic pain symptoms and health care utilization in women, 104 consecutive female patients presenting to a multidisciplinary pain center for management of chronic pain were surveyed. Outcomes included a measure of sexual or physical abuse history (Drossman Sexual-Physical Abuse Survey), and measures of anxiety, health care utilization, substance abuse, and somatic symptoms. Forty-eight percent of the sample reported a history of physical abuse (PA) or sexual abuse (SA). Forty percent of the abused patients reported both PA and SA and the remainder reported SA (37%) or PA (23%) alone. The women who reported abuse had increased pain, physical symptoms, anxiety symptoms, and mental health care utilization compared to nonabused women. The women who reported abuse were also more likely to smoke and abuse street drugs. Women who reported both PA and SA were more likely to report head pain when compared to those who reported only PA or SA. Given the impact of abuse, particularly SA, on the presentation of chronic pain, queries regarding abuse should become a routine component of the patient interview. Abused patients should be referred to mental health care practitioners as a component of successful pain management if unresolved issues persist.

Adolescent↗

Determination of the effective therapeutic dose of intrathecal sufentanil for extracorporeal shock wave lithotripsy.

UNLABELLED: Intrathecal (IT) sufentanil provides effective analgesia for extracorporeal shock wave lithotripsy. However, the optimal dose of sufentanil has not been established. We designed a prospective, randomized, double-blinded study to determine the optimal dose of IT sufentanil. Sixty men were randomized to receive 12.5,15,17.5, or 20 microg of IT sufentanil (n = 15 for each group) via a combined spinal epidural technique. Inadequate analgesia was treated with IV propofol, and the epidural was activated for a pain score greater than 6 on a 10-point verbal analog pain scale. Intraoperative and postoperative visual analog pain scale scores were significantly higher in the 12.5-microg group compared with 20-microg group (3.2 +/- 1.6 vs 1.6 +/- 1.2, P < 0.05, and 1.1 +/- 0.5 vs. 0.5 +/- 0.4, P < 0.05, respectively). The smaller-dosage groups of IT sufentanil required significantly more supplemental boluses of propofol compared with the 20-microg group (67%, 53%, and 40% vs 6%, respectively, P < 0.05). However, pruritus was significantly diminished in the smaller-dosage groups compared with the 20-microg group (55%, 60%, and 67% vs 100%, P < 0.05). The time to discharge was significantly shorter in the 15-microg group compared with the 20-microg group (84 +/- 40 min vs 126 +/- 48 min, P < 0.05). These results suggest that 15 microg of IT sufentanil may be the optimal IT dose for patients undergoing extracorporeal shock wave lithotripsy. IMPLICATIONS: Many anesthetic techniques are used for extracorporeal shock wave lithotripsy (ESWL). We have previously shown that intrathecal sufentanil was effective for ESWL, but was associated with a high incidence of itching. We tested 60 patients in four spinal sufentanil dose groups and found that doses of 15 and 17.5 microg provided the most effective analgesia with the fewest side effects for ESWL, with only mild itching.

Adolescent↗

Connexin expression in Huntington's diseased human brain.

In Huntington's diseased human brain, it is in the caudate nucleus (CN) and globus pallidus (GP) of the basal ganglia where nerve cell death is seen most dramatically. The distribution of five gap junction proteins (connexins 26, 32, 40, 43 and 50) has been examined in these areas in normal and Huntington's diseased human brain using immunohistochemical techniques. There was no Cx50 expression observed and Cx40 was localized in the endothelial cells of blood vessels, with the Huntington's diseased brains having more numerous and smaller blood vessels than normal tissue. Cx26 and Cx32 revealed a similar distribution pattern to each other in both normal and diseased brains with little labelling in the CN but clear labelling in the GP. Cx43, expressed by astrocytes, was the most abundant connexin type of those studied. In both normal and diseased brains Cx43 in the GP was homogeneously distributed in the neuropil. In the CN, however, Cx43 density was both increased with Huntington's disease and became located in patches. Glial fibrillary acidic protein(GFAP) staining of astrocytes was also highly increased in the CN compared with normal brains. These labelling patterns indicate a reactive astrocytosis around degenerating neurons with an increased expression of astrocytic gap junctions. The enhanced coupling state between astrocytes, assuming the junctions are functional, could provide an increased spatial buffering capacity by the astrocytes in an attempt to maintain a proper environment for the neurons, helping promote neuronal survival in this neurodegenerative disorder.

Animals↗

Connexin43 gap junction levels during development of the thoracic aorta are temporally correlated with elastic laminae deposition and increased blood pressure.

A characteristic property of the vascular smooth muscle cell is its ability to modulate between a contractile phenotype, responsible for control of vascular tone, through to a synthetic phenotype, capable of migration and synthesis of extracellular matrix molecules. Smooth muscle cells are coupled by gap junctions, the membrane structures which permit direct intercelluar passage of ions and small molecules, and which play a role both in electrical coupling and intercellular communication during patterning and development. We have previously found that connexin43 type gap junction expression is upregulated in the synthetic phenotype smooth muscle cell in vitro and during atherosclerotic plaque formation in human coronary arteries. On the basis of immunohistochemical labelling, confocal laser scanning microscopy and digital image analysis, we now report that relatively high levels of connexin43 are expressed during development of the rat thoracic aorta, temporally correlating with reported periods of smooth muscle cell proliferation and secretion of elastic laminae. A major peak in expression occurs at seven days post-natal, with a second less pronounced peak at 72 days post-natal. The principal peak in gap junction levels appears to coincide with increased post-natal blood pressure and aorta media thickening. The amount of gap junction labelling falls off to normal adult levels as the smooth muscle cells modulate towards the contractile phenotype and growth is completed. The results indicate an association between direct cell-to-cell communication and synthetic phenotype smooth muscle cell activity during aortic growth and patterning.

Animals↗

The role of irrigation in the development of hypothermia during laparoscopic surgery.

OBJECTIVES: Our purpose was to determine the incidence and etiology of hypothermia during laparoscopic surgery and to evaluate the role of irrigation fluid temperature. STUDY DESIGN: A prospective randomized study was performed of 35 women undergoing operative laparoscopy under general anesthesia who received surgical irrigation fluid either at ambient temperature or warmed to 39 degrees C. The core body temperature was determined with use of both an esophageal sensor and a tympanic membrane sensor and was expressed as the change from baseline. Additional data collected included age, height, weight, amount of irrigation fluid and intravenous fluid used, room temperature, length of anesthesia, and amount of carbon dioxide used for pneumoperitoneum. RESULTS: Hypothermia occurred in 94% of all patients, with no difference in incidence between the groups. The minimal core temperature was lower in the ambient temperature group (-1.7 degrees +/- 0.2 degrees C) than in the warmed fluid group (-1.0 degrees +/- 0.2 degrees C). Of the variables measured, length of anesthesia and the amount of ambient temperature fluid alone explained the drop in core temperature. CONCLUSION: Hypothermia is extremely common in laparoscopic surgery and is related to the length of anesthesia and the use of ambient temperature irrigation fluid. The use of warmed irrigation fluid can decrease, but not eliminate, this drop in core temperature.

Adult↗

Intrathecal sufentanil for extracorporeal shock wave lithotripsy provides earlier discharge of the outpatient than intrathecal lidocaine.

Many anesthetic techniques are currently used for extracorporeal shock wave lithotripsy (ESWL). This randomized, prospective, double-blind study was designed to examine postoperative recovery with two anesthetic techniques for unilateral ESWL; i.e., intrathecal sufentanil versus intrathecal 5% lidocaine. The incidence of adverse effects was also assessed. Twenty-two ASA physical status I-III patients, 18-70 yr of age who were scheduled for unilateral ESWL under spinal anesthesia were studied. Patients were randomized to receive either intrathecal sufentanil 20 microg + saline (n = 11) or intrathecal 5% lidocaine (n = 11) based on their height. Both patients and observers were blinded to the treatment groups. Patients were assessed for intraoperative and postoperative pain via a 10-cm verbal analog pain scale (VAPS) (0 = no pain, 10 = extreme pain). Stone sizes, number of shock waves, and voltages were also compared. The recovery profile-time to ambulate, void, oral intake, and home discharge-was documented. Antiemetic requirements in the postanesthesia care unit (PACU) and incidence of postoperative nausea and vomiting (PONV), pruritus, and sedation were also recorded. This study showed no differences in VAPS between groups at any time in the perioperative period. Patients who received intrathecal sufentanil ambulated (79 +/- 16 vs 146 +/- 57 min mean +/- SD; P < 0.05), voided (80 +/- 18 vs 152 +/- 54 min, P < 0.05), and were discharged home (98 +/- 17 vs 166 +/- 50 min, P < 0.005) significantly sooner than the patients who received intrathecal lidocaine. Although 27% (3 of 11) of the patients who received sufentanil reported pruritus, respiratory depression was not found. There were no differences in PONV between the two groups. Intrathecal sufentanil provided an enhanced recovery profile with significantly earlier home discharge when compared with intrathecal lidocaine. In conclusion, intrathecal sufentanil is a safe and effective method of anesthesia for outpatient unilateral ESWL.

Adjuvants, Anesthesia↗

Noncognitive disturbances in Alzheimer's disease: frequency, longitudinal course, and relationship to cognitive symptoms.

OBJECTIVE: To investigate the frequency and longitudinal course of symptoms of depression, agitation, and psychosis in a longitudinally studied sample of patients with Alzheimer's disease (AD). DESIGN: Longitudinal study of AD patients with follow-up assessments at 6-month intervals for an average of more than 3 years. SETTING: Alzheimer's Disease Research Center of the Mount Sinai Medical Center and the Bronx VA Medical Center, New York. PARTICIPANTS: A total of 153 AD patients. MEASUREMENTS: Blessed Test of Information, Memory and Concentration (BIMC) and the Alzheimer's Disease Assessment Scale cognitive (ADAS-Cog) and noncognitive (ADAS-NC) subscales. RESULTS: At entry into the study, more than 90% of patients had a behavioral disturbance that was rated as mild or worse on one of the 10 ADAS noncognitive items; and 40% had at least one rating that was moderate or severe. Correlational analyses indicated that, with the exception of the two mood-related items, noncognitive symptoms on the ADAS were not highly correlated with one another. Only one of the noncognitive items, concentration, was strongly correlated with the severity of cognitive impairment. On average, patients showed progressively worse cognitive functioning over time as measured both by the ADAS-Cog and the BIMC. The mean severity of noncognitive symptoms did not change during the course of a 5-year follow up. The severity of behavioral disturbance at any one evaluation was negatively correlated with change in behavior during the next 6 months and was not correlated with cognitive decline. CONCLUSION: Mild behavioral disturbances are common, whereas moderate to severe behavioral symptoms are less frequent in this population of AD patients. Disturbances in mood and manifestations of agitation and psychotic symptoms are not closely related to one another and show little progressive worsening over time. Rather, they tend to be episodic such that increasing severity at one time is usually followed by improvement later. Concentration problems are a manifestation of cognitive dysfunction rather than behavioral disturbance in AD. Implications of these results for treatment of noncognitive disturbances in AD are discussed.

Activities of Daily Living↗