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Biomedical subjects

E MacKenzie

Publications and source records attributed to E MacKenzie.

16 recordsLinked to original sources

The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein.

Many studies suggest that a multi-tissue tumour suppressor gene is located at human chromosome 7q31.1. We have cloned and characterized a novel gene at this locus. The TES gene lies within the minimal region of overlap of several LOH studies and appears to possess the properties of a tumour suppressor. TES is widely expressed and is predicted to encode a protein of 421 amino acids, with three C-terminal LIM domains. Mutation analysis of the coding TES exons in 21 human tumour-derived cell lines revealed the presence of a frameshift mutation in one allele in the breast cancer cell line ZR-75. Methylation of the CpG island at the 5' end of TES appears to be a remarkably frequent finding, occurring in seven out of 10 ovarian carcinomas and in each of the 30 tumour-derived cell lines tested. Moreover, forced expression of TES in HeLa or OVCAR5 cells, resulted in a profound reduction in growth potential, as determined by the colony formation assay. We believe that TES is a tumour suppressor gene that is inactivated primarily by transcriptional silencing resulting from CpG island methylation.

Base Sequence↗

Long-term physical impairment and functional outcomes after complex facial fractures.

To develop an understanding of the expected functional outcomes after facial trauma, a retrospective cohort study of patients with complex facial fractures was conducted. A cohort of adults aged 18 to 55 years who were admitted to the R. Adams Cowley Shock Trauma Center between July of 1986 and July of 1994 for treatment of a Le Fort midface fracture (resulting from blunt force) was retrospectively identified. Outcomes of interest included measures of general health status and psychosocial well being in addition to self-reported somatic symptoms. General health status was ascertained using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The Body Satisfaction Scale was used to define patient concerns about altered body image and shape. To determine whether complex maxillofacial trauma and facial fractures contributed to altered social interactions, the Social Avoidance and Distress scale was used. In addition, information about a patient, his or her injury, and its treatment were ascertained from the medical records. Using the methods described above, 265 patients with Le Fort fractures were identified. These individuals were matched to a similar group of 242 general injury patients. A total of 190 of the Le Fort patients (72 percent of those eligible for the study) and 144 (60 percent) general injury patients were successfully located, and long-term interview data were acquired.Le Fort fracture patients as a group had similar health status outcomes when compared with the group of general injury patients. However, when outcomes were examined by the complexity of the Le Fort fracture, the authors found that study subjects with severe, comminuted Le Fort injuries (group D) had significantly lower SF-36 scores (worse outcomes) for the two dimensions related to role limitations: role limitations due to physical problems and role limitations due to emotional problems (p < 0.05). SF-36 scores for all other dimensions except physical function were also lower for comminuted versus less complex Le Fort fractures, although differences were not statistically significant.Specifically, there was a direct relationship between severity of facial injury and patients reporting work disability. Of group C and D Le Fort patients (severely comminuted fractures) only 55 and 58 percent, respectively, had returned to work at the time of follow-up interview. These figures are significantly lower than the back-to-work percentage of patients with less severe facial injury (70 percent). When study participants were asked if they were experiencing specific somatic symptoms at the time of the interview that they had not experienced before the injury, a significantly larger percent of the Le Fort fracture patients (compared with the general injury patients) responded in the affirmative. Differences between the Le Fort fracture and general injury groups were statistically significant (p < 0.05) for all 11 symptoms. The percentage of patients reporting complaints increased with increasing complexity of facial fracture in the areas of visual problems, alterations in smell, difficulty with mastication, difficulty with breathing, and epiphora, and these differences reached statistical significance. Patients sustaining comminuted Le Fort facial fractures report poorer health outcomes than patients with less severe facial injury and substantially worse outcomes than population norms. It is also this severely injured population that reports the greatest percentage of injury-related disability, preventing employment at long-term follow-up. The long-term goal of centralized tertiary trauma treatment centers must be to return the patient to a productive, active lifestyle.

Activities of Daily Living↗

Determinants of disability after lower extremity fracture.

BACKGROUND: Factors influencing the progression of physical impairment to patient-perceived disability are not well known. We sought to better understand this relationship in the setting of injury. METHODS: We followed a cohort of 302 patients with lower extremity fractures over a 1-year period. Physical impairment was assessed by range of motion, strength, and pain. Range of motion and strength were assessed together as a proportion of normal function of the extremity (impairment score). Pain was assessed using a Visual Analogue Scale (VAS) pain score. Disability was assessed using the Sickness Impact Profile (SIP), a widely used measure of patient-perceived limitations of everyday activities attributable to illness. The SIP was administered during hospitalization to assess preinjury baseline. Impairment assessment and readministration of the SIP were performed at 12 months after injury. RESULTS: Impairment in leg function (range of motion and strength) was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 23% of the variance in overall SIP scores. Likewise, VAS pain score was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 29% of the variance in overall SIP scores. In a multivariate linear regression analysis, variables that were independently associated with overall SIP score included impairment score, VAS pain score, preinjury SIP, poverty status, education status, social support, having hired a lawyer, and involvement with workers' compensation. These variables accounted for 52% of the variance in overall SIP scores at 12 months. CONCLUSION: The degree of physical impairment accounts for only a small amount of the variance in disability from lower extremity fracture. Identifiable patient characteristics including age, socioeconomic status, preinjury health, and social support together with impairment account for over half of the variance in long-term disability. Further research is needed to increase understanding of other factors that influence the progression of impairment to disability, especially those factors that may be amenable to intervention.

Adolescent↗

Disabilities resulting from traffic injuries in Barcelona, Spain: 1-year incidence by age, gender and type of user.

The purpose of this study was to examine the 1-year incidence of disabilities resulting from traffic injuries among the population of Barcelona (Spain), as well as its distribution by age, gender and type of motor-vehicle user, taking into account different exposure criteria. This is a population-based cross-sectional study; subjects were all cases (n = 4080) having undergone a medical examination for a traffic injury having occurred in 1993 resulting in a disability among residents in the area of Barcelona. Subjects were considered to have suffered a disability as a result of an injury if they were prevented from carrying out their normal activities for a period of 2 days or more. In 1993, the cumulative incidence rate of disability was 237.9 cases per 100,000 inhabitants, higher for men (287.1) than for women (193.9). The 20-24 year age group showed the highest incidence of disability (607.5). The rate of incidence of disability was 95.5 per 100,000 inhabitants among occupants of two wheeled vehicles, 87.7 among car occupants and 39.9 in pedestrians. When length of exposure to traffic was taken into account, the incidence rate of disability for residents aged > 14 years was 1.09 per 100,000 hours per person per year, similar for both sexes. This study represents a first attempt to use population-based health data to evaluate the incidence of disabilities due to traffic injuries. The results allow the identification of the groups with the greatest risk and who contribute the most to disabilities resulting from injuries, especially young users of two-wheeled motor vehicles.

Accidents, Traffic↗

Cultural competence--an essential hybrid for delivering high quality care in the 1990's and beyond.

Establishing guidelines for culturally competent medical care will help all physicians to fulfill their mandate to meet the health care needs of the individual patient as well as of patient populations, and to lower costs by encouraging a healing partnership with the patient, thus increasing patient responsibility for his or her own health. Being culturally sensitive is not enough. Nor is simply classifying patients according to race adequate. Many researchers in social science and health services increasingly agree that race in our heterogeneous U.S. population has limited biological meaning and more often than not is just a poor proxy for culture or socioeconomic status. Guidelines and quality indicators that seek to measure and improve cultural competence must take into account, in an integrated fashion, these three necessary components in the delivery of high-quality services to populations: 1) the health-related cultural factors; 2) the incidence and prevalence of diseases in the population; and 3) treatment outcomes peculiar to that population. To be culturally competent is to incorporate and integrate these critical factors into caring for diverse populations. If health care systems, individually and collectively, are to provide care of high quality that is cost-effective to all populations, researchers and funders of research must invest in an aggressive agenda that pursues two directions: the validation of existing quality indicators in minority populations, and the development of new quality indicators that assess the organization's ability to develop culturally competent care. Only in this way will those of us in the medical profession be able to fulfill our calling to relieve suffering without discriminating against some populations.

Clinical Competence↗

The Sickness Impact Profile as a tool to evaluate functional outcome in trauma patients.

Because the ultimate goal of trauma care is to restore injured patients to their former functional status, reliable evaluation of functional status is needed to assess fully the effectiveness of trauma care. We hypothesized that the Sickness Impact Profile (SIP), a widely used measure of general health status, would be a useful tool to evaluate the long-term functional outcome of trauma patients and that the SIP would identify unexpected problems in the recovery process and groups of patients at high risk for long-term disability. A prospective cohort of 329 patients with lower extremity fractures admitted to three level I trauma centers were interviewed using SIP at 6 and 12 months postinjury. Patients with major neurologic injuries were excluded. Overall SIP scores and each of the component subscores may range from 0 (no disability) to 100. In this series, the mean overall SIP was 9.5 at 6 months and 6.8 at 12 months, compared with a preinjury baseline of 2.5. At 12 months, 52% of patients had no disability (SIP 0 to 3), 23% mild disability (4 to 9), 16% moderate disability (10 to 19), and 9% severe disability ( > or = 20). Disability was widely distributed across the spectrum of activities of daily living, including physical functioning (mean score of 5.5), psychosocial health (mean score of 5.5), sleeping (mean score of 10.0), and work (mean score of 21.0). The SIP scores did not correlate with Injury Severity Score.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

ABL-BCR mRNAs transcribed from chromosome 9q+ in Philadelphia-chromosome-positive chronic myeloid leukaemia.

Polymerase chain reaction amplification of reverse transcription products has demonstrated the presence of abl-bcr hybrid mRNAs in RNA from peripheral blood leucocytes of Philadelphia-chromosome-positive chronic myeloid leukaemia patients; such hybrid mRNAs can contain either of the alternative first exons of c-abl. A survey of 12 CMLs has shown that abl-bcr mRNAs occur in the leucocytes of some, but not all, patients, and that they are present both in chronic-phase and acute-phase leucocytes.

Base Sequence↗

Progress in characterizing anatomic injury.

A three-valued description of anatomic injury is presented. Anatomic profile (AP) components A, B, and C summarize serious injuries (greater than AIS 2) to the head/brain or spinal cord; to the thorax or front of the neck; and all remaining serious injuries. Relationships between AP components and survival rate reaffirm the seriousness of head injury. Logistic function models relating AP components and the Injury Severity Score (ISS) to survival probability were based on 20,946 Major Trauma Outcome Study (MTOS) patients (9.2% mortality rate) submitted through 1986. Model performance comparisons were based on 5,939 MTOS patients (7.8% mortality rate) submitted during 1987. The AP better discriminated survivors from nonsurvivors and provided a 31% increase in sensitivity when compared with the ISS. Neither the ISS nor the AP alone reliably predict patient outcome. The predictive power of methods for estimating patient survival probability which include physiologic indices or profiles, patient age, and an anatomic profile should be compared with current methods. The AP, which is based on the severity and location of all serious injuries, provides a more rational basis for comparing patient samples than the ISS.

Humans↗

Reproducibility of the diagnosis of cervicitis in pregnancy.

Cervicitis has been associated with several infections of the female genital tract. Criteria have been established for making the diagnosis of cervicitis in gynecologic populations but there are no well-established criteria for diagnosing cervicitis in obstetrical populations. Because of the association of the cervicitis and sexually transmitted diseases, and because of the association of sexually transmitted diseases and adverse pregnancy outcome, the present study was undertaken in an attempt to establish criteria for the diagnosis of cervicitis in pregnancy. We also attempted to determine the reproducibility of that diagnosis with respect to intra- and interobserver variability. We concluded that intraobserver variability is improved after specific training has been completed and that interobserver variability may be reduced to an acceptable level. On a public health scale, this may allow for identification of a population at high risk for adverse pregnancy outcome when sophisticated microbiologic techniques are unavailable.

Adolescent↗

Effects of topical application of a calcium antagonist (nifedipine) on feline cortical pial microvasculature under normal conditions and in focal ischemia.

Cat cortical arterioles and venules were exposed in vivo to the Ca2+ antagonist nifedipine under normal conditions and in focal ischemia. Topical application of nifedipine caused a marked, concentration-dependent arteriolar dilatation. The dilatatory responses increased significantly with decreasing arteriolar size. Perivenular microapplication of nifedipine invariably caused dilatation that was less pronounced but more long-lasting than that on the arteriolar side. Arterioles, which constricted after middle cerebral artery occlusion, invariably dilated following nifedipine application. These dilatatory responses were transient but could be repeated, and on some occasions were accompanied by a return of flow in vessels in which stasis had been present. The results suggest that nifedipine is able to dilate cerebral vessels both under normal conditions and when contracted during focal ischemia.

Animals↗

Role of Franzen needle aspiration biopsy in carcinoma of the prostate.

A retrospective study is reported of all Franzen fine-needle aspiration cytology undertaken at Southmead Hospital between January 1978 and December 1981. A total of 1043 aspirates were examined from 753 patients. The diagnosis of carcinoma of the prostate was missed in 2 patients. Twenty-one patients with cytologically-proven carcinoma in histologically-benign prostates were detected, and the role of the Franzen needle in the diagnosis of early prostatic cancer is discussed. Of the 218 patients proceeding to prostatectomy, there were 91 patients with carcinoma and in 65 (72%) the cytological and histological grading was identical. A significant disparity occurred in 8 cases and the reasons are discussed.

Biopsy, Needle↗

Validity and reliability of the dexter hand evaluation and therapy system in hand-injured patients.

This study compares measurements obtained using the Dexter Hand Evaluation and Therapy System with those obtained using manual goniometers and grip and pinch dynamometers. Intrarater and inter-rater reliabilities for each tool were also examined. Repeated digit range of motion and strength measurements were performed on 30 subjects who had prior upper extremity injuries. Three therapists performed all measurements on each subject three times, using both Dexter and manual instruments. Analyses of variance (ANOVAs) and intraclass correlation coefficients (ICCs) were used to assess concurrent validity and therapist reliability. The findings show that the computerized Dexter finger goniometer and grip and pinch dynamometers provide measurements that are statistically similar to those of their manual counterparts. The ANOVA results for concurrent validity showed no significant differences between mean measurement values across therapists for the Dexter tools compared with the manual tools (p> or =0.54). In addition, no significant differences were found among or between the therapists' measurements. The range of ICCs for intrarater and inter-rater reliability for all four tests was 0.86 to 0.99. However, a two-way ANOVA revealed a therapist effect during pinch strength measurements (p< or =0.05), suggesting the need for same-therapist and same-tool measurements until the Dexter pinch dynamometer has been further evaluated.

Adult↗

Vasomotor effects of dimethyl sulfoxide on cat cerebral arteries in vitro and in vivo.

We studied the direct vascular effects of dimethyl sulfoxide (DMSO) in isolated middle cerebral arteries and on pial arteriolar caliber after subarachnoid perivascular microinjection in chloralose-anesthetized cats, and on brain retraction in cats given DMSO intravenously. DMSO did not constrict isolated cerebral arteries at any of the concentrations studied (10(-10) to 4 X 10(-1) M). In middle cerebral arteries precontracted with potassium, 5-hydroxytryptamine, prostaglandin F2 alpha, or with mechanically raised tone, DMSO at concentrations of 10(-10) to 10(-2) M had no significant effects; at concentrations greater than 10(-2) M, DMSO consistently relaxed the arteries, probably because of the hyperosmolarity of the bathing solution. Microapplication of DMSO (10(-6) to 10(-2) M) around pial arterioles on the cortical surface did not change arteriolar caliber significantly. Higher concentrations of DMSO (1%) increased arteriolar caliber by 56 +/- 4% (p less than 0.001), probably as a consequence of solution hypertonicity. DMSO did not modify in vivo cerebrovascular responses to alterations in perivascular potassium ion concentrations. Intravenous administration of DMSO did cause obvious brain shrinkage. These data provide no support for the view that direct cerebral vascular effects play a major role in the clinical efficacy of DMSO, but are consistent with the hypothesis that DMSO's ability to lower intracranial pressure derives from its osmotic effect on cerebral issue.

Animals↗

Black-white differences in alcohol use by women: Baltimore survey findings.

Although black women suffer disproportionately from alcohol-related illnesses and causes of death, little is known about the extent to which poorer outcomes are a function of differences in drinking, the use of health services, or some combination of these factors. This study, using interview data obtained in the Baltimore Epidemiologic Catchment Area household survey, compares racial differences in alcohol use and abuse among a sample of 2,100 women. After controlling for differences in sociodemographic characteristics, black women were found to be at no greater risk than whites for heavy drinking or for suffering from alcohol abuse or dependence. Racial differences, however, were observed in heavy drinking by years of education. A similar percentage of black women and white women who had not completed high school were heavy drinkers, but black women with 12 or more years of education were less likely to be heavy drinkers than whites with comparable education. These findings raise questions about the extent to which differences in drinking contribute to the poorer alcohol-related health outcomes of black women in Baltimore. Additionally, the finding that education was inversely related to heavy drinking among black women may be helpful in shaping early alcohol abuse intervention and treatment services that target black women.

Adolescent↗