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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 91 records · Page 5Linked to original sources

Serotonin-induced increases in platelet cytosolic calcium concentration in depressed, schizophrenic, and substance abuse patients.

Exaggerated intracellular calcium responses to challenges with serotonin (5-HT) have been reported in depression. In our studies, consistent with previous reports, patients with depression exhibited an exaggerated increase in 5-HT-stimulated intracellular calcium concentration ([Ca++]i). Basal cytosolic calcium was elevated in both calcium-free and 1 mM calcium media in depressed patients. the increased responsiveness to 5-HT was seen in both conditions. Patients with schizophrenia and substance abuse did not differ from normal controls. The 5-HT response was correlated with diastolic blood pressure (r = 0.33, p = 0.02): however, this association did not fully account for the exaggerated [Ca++]i responses in the depressed group. These findings suggest that exaggerated increases in [Ca++]i in response to serotonin are a characteristic of depressed patients not shared with schizophrenic and substance abuse patients. The relationship of depression to hypertension, two conditions that share abnormalities of calcium homeostasis, warrants further study.

Adult↗

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations.

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220-expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.

Alleles↗

Use of a type-III trilateral external skeletal fixation device in three deer with comminuted fractures.

A type-III trilateral external skeletal fixation device was used to repair comminuted fractures of metacarpal and tibial bones in 3 deer. Mean weight of the deer was 25 kg, and mean age was 4 months. Mean interval from application until removal of the device was 6.5 weeks. All deer had complete function of their previously fractured limbs and had minimal complications during healing. Several factors should be considered when choosing a method of repair for wildlife with fractured limbs. Economic constraints and demeanor of the animal may limit the number of options. Analysis of results of our findings indicated that type-III trilateral external skeletal fixation devices can be used for the repair of comminuted fractures in young deer.

Animals↗

Obesity in the Caribbean.

People of African origin who live in the Caribbean share a common genetic heritage but live in socioeconomic environments that diverge widely. A cross-cultural study of males and females from Jamaica, St. Lucia and Barbados investigated the prevalence of hypertension and its environmental determinants. Standardized measurement techniques allowed comparable measurements of weight, height, waist and hip circumferences, and blood pressure. The population values for body mass index (BMI), per cent overweight (males BMI > or = 27.8 kg/m2; females BMI > or = 27.3 kg/m2) and per cent obese (males BMI > or = 31.1 kg/m2; females BMI > or = 32.3 kg/m2) are presented. Prevalence of hypertension is based on the age-adjusted total population. The gradient in per capita gross national product in Jamaica, St. Lucia and Barbados parallels the gradient in the proportions of population in those countries who are obese. BMI explained 26% of the variance in blood pressure in females and 13% in males. Obesity is a significant problem in the Caribbean, as it is in many other developing countries, and it is associated with a high prevalence of hypertension, particularly in women.

Body Composition↗

Obesity in peoples of the African diaspora.

People of African descent in the Caribbean and the USA originated from the Bight of Benin in West Africa. Although these populations share a common genetic heritage, they now live under different socioeconomical conditions. Assuming genetic similarity, a cross-cultural examination of these peoples in West Africa, the Caribbean and the USA may attenuate the effect of genetic factors and allow the assessment of environmental contributions to a biological outcome. We carried out an epidemiological survey to determine the prevalence of hypertension and the contribution of risk factors to the variation in blood pressure. We measured the height, weight, waist and hip circumferences, and blood pressure of adults in Nigeria, Cameroon, Jamaica, St. Lucia, Barbados and the USA. In urban populations there was a trend towards increasing weight, height, body mass index, and proportions of those overweight and obese going from West Africa to the USA, with the Caribbean being intermediate. The prevalence of hypertension lay on a similar gradient. Given a common genetic susceptibility, urbanization and western acculturation are therefore associated with increasing hypertension and obesity.

Adult↗

Physicochemical and metabolic basis for the differing neurotoxicity of the pyrrolizidine alkaloids, trichodesmine and monocrotaline.

Monocrotaline and trichodesmine are structurally closely related pyrrolizidine alkaloids (PAs) exhibiting different extrahepatic toxicities, trichodesmine being neurotoxic (LD(50) 57 mu mol/kg) and monocrotaline pneumotoxic (LD(50) 335 mu mol/kg). We have compared certain physicochemical properties and metabolic activities of these two PAs in order to understand the quantitative and qualitative differences in toxicity. Both PAs were metabolized in the isolated, perfused rat liver to highly reactive pyrrolic dehydroalkaloids that appear to be responsible for the toxicity of PAs. More dehydrotrichodesmine (468 nmol/g liver) than dehydromonocrotaline (116 nmol/g liver) was released from liver into perfusate on perfusion for 1 hr with 0.5 mM of the parent PA. Dehydrotrichodesmine had a significantly longer aqueous half-life (5.4 sec) than that of dehydromonocrotaline (3.4 sec). In vivo, significantly higher levels of bound pyrroles were found in the brain 18 hr after injection of trichodesmine (25 mg/kg; i.p.) than were seen following either an equal dose (25 mg/kg; i.p.) or an equitoxic dose (90 mg/kg; i.p.) of monocrotaline. Trichodesmine had a higher partition coefficient than monocrotaline for both chloroform and heptane, indicating its greater lipophilicity. The pK(a) of trichodesmine (7.07) was only slightly higher than that of monocrotaline (pK(a¿ 6.83), suggesting that a difference in degree of ionization was not a major factor affecting the relative ability of the dehydroalkaloids to cross the blood-brain barrier. We conclude that the greater lethality and neurotoxicity of trichodesmine compared to monocrotaline is due to two structural characteristics: (i) steric hindrance at position 14 of dehydrotrichodesmine results in greater resistance to hydrolysis, allowing more to be released from the liver and to be delivered to the brain; (ii) the larger isopropyl substituent at position 14 of dehydrotrichodesmine renders the molecule more lipophilic, leading to greater penetration of the brain.

Alkaloids↗

Three years of an adult burns support group: an analysis.

A retrospective analysis, by survey, of the benefits of a support group and preference for its structure is presented. Psychosocial support after burn injury is identified as important and a support group is recommended as being routine in the aftercare for burns' patients.

Adult↗

Standardization of blood pressure measurement in an international comparative study.

In the context of a collaborative study on the epidemiology of hypertension in populations of West African origin procedures for standardization of the measurement of blood pressure were evaluated. Comparisons of mean levels of blood pressure, which in large part determine prevalence rates, are highly sensitive to differences in technique. While rotating a single field team may be the ideal approach to multisite studies, it is not practical in international collaborative research. Appropriate techniques to standardize multiple teams over a long period of time have not been well developed, however. In the present study 8981 individuals were examined in eight sites in six countries with the standard mercury sphygmomanometer. An evaluation of the effectiveness of central training, site visits, monitoring of digit preference, and the use of an electronic device for internal standardization is described. In all but one of the sites reliability was high and comparable to the observers at the Coordinating Center. Digit preference for the entire set of measurements was limited (frequency of terminal zero = 23.5% for systolic and 28.9% for diastolic readings) and could be shown to have virtually no effect on prevalence rates or correlation estimates. Mean differences among observers within a given site and between sites were small (+/- 0-5 mmHg). While logistically complex, these methods can provide the basis for standardization in international comparative blood pressure surveys.

Adult↗

Neonatal and pediatric critical care: ethical decision making.

The current standards for surrogate decision making for children are analyzed in this article. A number of potential pitfalls are involved with this issue, including questions about the child's maturity and competence. The present approach for medical decision making for noncompetent children is the "best interest" standard. In many medical decisions, the "best interest" standard is not applicable and a "rational parent" standard is presented.

Child↗

Patterns of comorbidity and mortality risk in blacks and whites.

Comorbidity, the co-existence of multiple chronic conditions in a single individual, has been shown to modify the prognosis of disease states. To estimate disease burdens within and among racial subpopulations of the United States, we examined cross-sectional patterns of comorbidity and their impact on survival using data from the NHANES-1 Epidemiologic Follow-up Study (NHEFS). We considered the occurrence of four cardiovascular conditions: stroke, coronary heart disease, hypertension and diabetes. We summarize the joint occurrence of these four conditions using these different methodologies: the number of conditions occurring in each individual and two summaries that weight the conditions according to their prognostic significance. Using all three methodologies, we found an excess burden of chronic disease in black women as compared with white women. Black men had an excess burden compared to white men for the first two methodologies. However, when we model the relationship of the joint occurrence of the conditions to subsequent mortality, black men and white men are seen to have a similar burden. This similarity of black and white men is due to an interaction between race and prevalent stroke in men that we hypothesize may be due to the small number of black men available for study. Given the apparent conditioning effect of co-existing diseases, it is evident that estimation of disease burdens among groups that differ in terms of health status, in particular among U.S. blacks and whites, requires accounting for the occurrence of multiple chronic diseases. Using either the number of conditions or the prognosis weighted summary, we demonstrated a higher burden of the conditions considered in blacks that in whites in a sample of the U.S. population.

Adult↗

Pain after craniotomy. A time for reappraisal?

Pain and nausea were prospectively assessed in 52 patients following elective craniotomy. When assessed at 6-hourly intervals the mean pain scores in patients during the first 24 h for all types of craniotomy were relatively low. However, for a period of at least 2 h 18% of patients complained of excruciating pain, 37% of patients complained of severe pain, 29% of patients complained of moderate pain, 4% of patients complained of mild pain and only 12% of patients complained of no pain in the 24 h following craniotomy. The mean dose of codeine phosphate used within the study period was 123 mg (SD 81). No statistically significant differences in severity of pain or use of codeine phosphate were found when comparing patients undergoing craniotomy at different sites. For at least 2 h 37% of patients complained of severe nausea or vomiting, 35% of patients complained of moderate nausea and only 29% of patients reported no symptoms of nausea during the 24-h study period. Again, no statistically significant differences were found in the severity of emetic symptoms when comparing patients undergoing craniotomy at different sites. Contrary to standard assumptions, severe or moderate pain in the first 24 h after craniotomy is common and is poorly treated with codeine phosphate alone.

Adolescent↗

Angiotensinogen and blood pressure among blacks: findings from a community survey in Jamaica.

OBJECTIVE: To examine the association between blood pressure, angiotensinogen levels, angiotensin converting enzyme activity and polymorphisms of the angiotensinogen and angiotensin converting enzyme genes in a population-based sample. METHOD: Five hundred participants were recruited in a house-to-house survey of three communities in metropolitan areas of Kingston and St Andrew, in Jamaica. Demographic data, anthropometric and blood pressure measurements were obtained for each participant during a brief clinic visit. Circulating levels of angiotensinogen and angiotensin converting enzyme activity were measured in venous blood samples. Polymorphisms of the angiotensinogen and angiotensin converting enzyme genes were determined. RESULTS: A weak association between angiotensinogen level, angiotensin converting enzyme activity and blood pressure was identified in this population, but substantial joint effect of angiotensin converting enzyme activity and angiotensinogen level on blood pressure was apparent. Variants of the angiotensinogen gene had inconsistent effects on blood pressure and on the risk of hypertension. Angiotensinogen level and angiotensin converting enzyme activity were significantly related to several measures of obesity, including body mass index, waist circumference and skin fold thickness. CONCLUSION: The angiotensinogen and angiotensin converting enzyme genetic variants which were studied appear to have only a modest relationship with blood pressure and associated anthropometric risk factors among blacks.

Adult↗

Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate.

We have performed a prospective randomised trial of 30 patients undergoing craniotomy to compare intramuscular codeine phosphate with patient-controlled analgesia using morphine 1 mg bolus with a 10-min lockout and no background infusion. For 24 h postoperatively, pain, nausea, Glasgow coma score, respiratory rate and sedation score were assessed. There was a wide variation in the amounts of morphine requested by the patients in the patient-controlled analgesia group in the first 24 h postoperatively (range 2-79 mg, median 17 mg). There was a small, but non-significant, reduction in pain scores in the patient-controlled analgesia group. There were no significant differences between the two groups in respect of nausea and vomiting, sedation score or respiratory rate. No major adverse effects were noted in either group. Patient-controlled analgesia with morphine is an alternative to intramuscular codeine phosphate in neurosurgical patients which merits further investigation.

Adolescent↗

Polymorphisms of renin-angiotensin genes among Nigerians, Jamaicans, and African Americans.

Within the context of an international collaborative study of the evolution of hypertension in the black diaspora, we determined the allelic distribution of hypertension candidate genes for the renin-angiotensin system in three populations of African origin. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and the M235T and T174M variants of the angiotensinogen (AGT) gene were examined in individuals from Nigeria, Jamaica, and the United States. Large differences in the prevalence of hypertension were recorded in door-to-door surveys, ranging from 16% in Nigeria to 33% in the United States. The frequency of the D allele was similar in all groups (54%, 59%, and 63% in Nigeria, Jamaica, and the United States, respectively). The 235T allele of the AGT gene was found in 81% of US and Jamaican blacks and 91% of Nigerians; very little variation was seen for the T174M marker. Despite large differences in hypertension rates, genetic variation at the index loci among these groups was modest. Overall, the frequency of the ACE*D allele was only slightly higher than that reported for European and Japanese populations, whereas the AGT 235T allele was twice as common. Compared with blacks in the western hemisphere, Nigerians had a higher frequency of the 235T allele, which is consistent with 25% European admixture in Jamaica and the United States. The results indicate the potential for etiologic heterogeneity in genetic factors related to hypertension across ethnic groups while suggesting that environmental exposures most likely explain the gradient in risk in the comparison among black populations.

Alleles↗