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Biomedical subjects

S Engel

Publications and source records attributed to S Engel.

At least 19 recordsLinked to original sources

Colour tuning in human visual cortex measured with functional magnetic resonance imaging.

The primate retina contains three classes of cones, the L, M and S cones, which respond preferentially to long-, middle- and short-wavelength visible light, respectively. Colour appearance results from neural processing of these cone signals within the retina and the brain. Perceptual experiments have identified three types of neural pathways that represent colour: a red-green pathway that signals differences between L- and M-cone responses; a blue-yellow pathway that signals differences between S-cone responses and a sum of L- and M-cone responses; and a luminance pathway that signals a sum of L- and M-cone responses. It might be expected that there are neurons in the primary visual cortex with response properties that resemble these three perceptual pathways, but attempts to find them have led to inconsistent results. We have therefore used functional magnetic resonance imaging (fMRI) to examine responses in the human brain to a large number of colours. In visual cortical areas V1 and V2, the strongest response is to red-green stimuli, and much of this activity is from neurons receiving opposing inputs from L and M cones. A strong response is also seen with blue-yellow stimuli, and this response declines rapidly as the temporal frequency of the stimulus is increased. These responses resemble psychophysical measurements, suggesting that colour signals relevant for perception are encoded in a large population of neurons in areas V1 and V2.

Brain Mapping

hsp47 and hsp70 gene expression is differentially regulated in a stress- and tissue-specific manner in zebrafish embryos.

We have examined differences in the spatial and temporal regulation of stress-induced hsp47 and hsp70 gene expression following exposure of zebrafish embryos to heat shock or ethanol. Using Northern blot analysis, we found that levels of hsp47 and hsp70 mRNA were dramatically elevated during heat shock in 2-day-old embryos. In contrast, ethanol exposure resulted in strong upregulation of the hsp47 gene whereas hsp70 mRNA levels increased only slightly following the same treatment. Whole-mount in situ hybridization analysis revealed that hsp47 mRNA was expressed predominantly in precartilagenous cells, as well as several other connective tissue cell populations within the embryo following exposure to either stress. hsp70 mRNA displayed a very different cell-specific distribution. For example, neither stress induced hsp70 mRNA accumulation in precartilagenous cells. However, high levels of hsp70 mRNA were detectable in epithelial cells of the developing epidermis following exposure to heat shock, but not to ethanol. These cells did not express the hsp47 gene following exposure to either of these stresses. The results suggest the presence of different inducible regulatory mechanisms for these genes which operate in a cell- and stress-specific manner in zebrafish embryos.

Amino Acid Sequence

Functional outcomes attained by T9-12 paraplegic patients with the walkabout and the isocentric reciprocal gait orthoses.

OBJECTIVE: To compare the functional outcomes attained by persons with paraplegia using the Walkabout Orthosis (WO) and the Isocentric Reciprocal Gait Orthosis (IRGO). DESIGN: A randomized crossover design. PATIENTS: Ten subjects with complete lesions between T9-T12. INTERVENTIONS: Over two 8-week periods, subjects were taught to use each orthosis in conjunction with elbow crutches. MAIN OUTCOME MEASURES: After each 8-week training period, subjects were assessed on their ability to perform five different sets of key skills associated with functional ambulation. RESULTS: There were no differences between orthoses in the ability of subjects to don and doff the orthoses, get up and down stairs and curbs, or walk on a flat surface. Subjects required significantly more assistance when using the WO to walk over inclined surfaces (median IRGO = "independent," median WO = "minimal assistance"; p = .03) but less assistance when using the WO to get from sitting to standing and standing to sitting (median IRGO = "moderate assistance," median WO = "minimal assistance"; p = .03). In addition, subjects walked significantly faster with the IRGO both on the flat (mean IRGO = .34 m/sec +/- .18, mean WO = .14 m/sec +/- .12; p = .002) and on inclined surfaces. CONCLUSIONS: Although it is easier to stand up and sit down with the WO, the IRGO facilitated a faster and more independent gait. Neither orthosis enabled subjects to be fully independent in the key skills necessary for functional ambulation after 8 weeks of training.

Activities of Daily Living

A comparison of the attitude of paraplegic individuals to the walkabout orthosis and the isocentric reciprocal gait orthosis.

This study compared the attitude of paraplegic individuals to the Isocentric Reciprocal Gait Orthosis (IRGO) and the Walkabout Orthosis (WO), after they had been given the opportunity of using both. Ten complete T9-12 paraplegic patients participated in this randomised cross-over design. Initially the subjects learned to walk with the first orthosis before taking it home for a 14 week home trial period. The same process of training an trialing the orthosis at home was then repeated with the second orthosis. Attitudes to specific aspects of the orthoses were assessed by an 18 point questionnaire and overall attitudes were inferred after determining the amount of time that subjects used the orthoses at home and determining which orthosis the majority of subjects wanted to keep at the end of the study. The main finding was that subjects did not perceive any significant differences between the two orthoses. That is: (i) the questionnaire did not detect significant differences in attitudes to the two orthoses; (ii) there was no significant difference in the number of subjects tat preferred one orthosis to the other, at the end of the study, and (iii) subjects did not derive more use from one orthosis than the other over the two 14 week home trial periods. In addition, it was found that few subjects wore either orthosis more than once every 2 weeks and that subjects were primarily using the orthoses for therapeutic purposes. This latter finding was supported by the results of the questionnaire that revealed that subjects found both orthoses to be useful for standing but not useful for performing more purposeful tasks. It was concluded that when subjects are primarily using the WO and IRGO for therapeutic purposes, they do not readily perceive differences between the two.

Adult

[Mortality and functional limitations in chronic patients: results of a follow-up study of elderly patients after myocardial infarct].

Long-term care is considered to be a major social medical problem in the elderly. Empirical data about mortality and functional deficits in every-day life is sorely needed for service programme management, planning, and health care policy-making. To set up an example for chronically diseased persons a follow-up study was conducted on patients suffering from coronary heart disease. The figure of 1710 probands who had survived their first myocardial infarction at an age of 60 to 74 during the time period from 1985 to 1992 was based on the register of acute coronary events with reference to the population of Augsburg, Germany. The probands were followed up in 1995. Hence, the observation time ranged from 2 to 10 years. 832 subjects (261 women, mean age 73.3; 571 men, mean age 71.9) were interviewed using a standardised questionnaire (net response rate 79%). 641 (37%) had died. The observed survival rates per year, which had been estimated by the life table method, were almost constant (93-95%) with the exception of the first 2 years (90%). Unexpectedly, the survival rates were not sex-related, but dependent on the age at the time of event. Nearly 60% out of the patients aged 60-64 (n = 577) and 40% out of the persons aged 70-74 (n = 567) survived for at least 10 years. On being asked to describe their health status, about 75% of the age group 60-64 and 65% of the age group 70-74 rated their general health to be at least fair, independent of the years already survived after myocardial infarction. Women reported worse overall health than men. To assess the functional status a short questionnaire recommended as valid by the Organization of Economic Cooperation and Development, was applied (OECD-Index). This indicator focuses on sensory deficits and mobility-related dysfunctions. Apart from impaired hearing, all self-reported deficiencies occurred more often in women than in men. This difference could not be observed in the group of probands older than 80. According to the OECD-definition 44% of the subjects (57% of the females, 38% of the males) were classified as disabled. The disabled probands differed from the non-disabled significantly in subjective complaints and major geriatric symptoms (e.g. pain, incontinence). The findings of this study support the already suggested purpose to employ both health outcome variables-the self-rated health and the functional status by OECD-as a comparable standard for population surveys.

Activities of Daily Living

Expression of microglial markers in the human CNS after closed head injury.

The loss of neurons after severe closed head injury is not only a consequence of the primary impact but also of secondary damage mechanisms. Among the cell population of the central nervous system microglia is surely a candidate to influence secondary damage mechanisms by releasing cytotoxic cytokines [1]. About microglial reaction in closed traumatic brain injury (TBI), however, no data are available. In contrast to experiments using stab wound injury the covering of the CNS in closed TBI are still intact. We have examined 17 patients who died because of TBI after various times post injury. We studied the expression of antigens which are either permanently present on microglial cells or those which are only facultatively found on activated microglia. Low numbers of microglial cells were shown to express MHC-class II antigens immediately after TBI which is also true for CD 68 and leukocyte common antigen (LCA). Surprisingly, however, antigens such as HAM 56 were expressed not earlier than 72 hours after TBI as well as the lectin ricinus communis agglutinin-1 (RCA-1). The results indicate a delayed activation of microglia in traumatic brain injury.

Adolescent

Determination of gaseous and dissolved oxygen in a closed fat cell culture system.

A novel method facilitates the determination of O2 content in the gas phase and in the culture medium of closed cell culture systems: Total O2 was swept out for 3 min by a stream of N2 under atmospheric pressure and carried to the measuring unit of a PBI Dansensor TIA-111-LV oxygen sensor, creating a peak-shaped signal, which was integrated over time. From the peak area, gas flow (determined by a Rotameter flow meter), and actual gas pressure and temperature, O2 content was calculated. The precision of the method was 1.1% (CV), recovery was 97.7%. O2 uptake was measured in white adipocytes, isolated by the collagenase method and cultured in a 3D matrix of agarose gel. As a basis of reference, DNA content of the cultures (9.5 pg/cell) was determined by a fluorimetric method. The viability of the cells was not affected by O2 determination, as shown by the maintenance of cellular adenine nucleotide content during the analytic procedure. The decline of O2 content in the cultures was constant over 72 h. The mean rate of cellular O2 consumption was 34.1 mumol/micrograms DNA.h.

Adipocytes

Assessment of documented foot examinations for patients with diabetes in inner-city primary care clinics.

BACKGROUND: The established guidelines for a diabetes foot examination include assessing circulatory, skin, and neurological status to detect problems early and reduce the likelihood of amputation. OBJECTIVE: To determine documented adherence with guidelines for foot examinations. SETTING: Four clinics in underserved areas. METHODS: Charts of 350 diabetic patients, identified by billing code, were reviewed for foot examination documentation. A documented foot examination was defined as assessing at least two of the three components of a foot examination. The review determined the periodicity and prevalence of foot examinations, referrals to a podiatrist or vascular surgeon during a 2-year period, and risk factors for foot complications. Stepwise logistic regression was used to determine whether risk factors for foot complications predicted foot examination status. RESULTS: The patients had a mean age and duration of diabetes of 57.7 and 8.8 years, respectively; 86% were black or Hispanic. There was no indication of foot examination or referral for 55.7% of the patients during the 2-year period. Patients with foot care referrals were more likely to have foot examinations by their primary care providers (P = .0001). There was almost a fourfold increase in the odds that patients with diagnosed peripheral vascular disease had foot examinations, with twofold greater odds for each 25-year increase in age. CONCLUSIONS: Populations at risk of diabetic complications are unlikely to have foot examinations in their primary medical care, but having peripheral vascular disease increases the likelihood. Efforts are needed to improve adherence to foot examination guidelines for patients with diabetes from underserved populations.

Ambulatory Care Facilities

Soft drugs. 19. Pharmacokinetics, metabolism and excretion of a novel soft corticosteroid, loteprednol etabonate, in rats.

PURPOSE: Pharmacokinetics, metabolism and excretion of loteprednol etabonate (LE) were investigated in rats. METHODS: The pharmacokinetic studies were performed by iv injections of LE (1-20 mg/kg). In the metabolism and excretion studies, 0.5-10 mg/kg of LE were iv administered, bile and urine samples were collected for 6 hr. RESULTS: The pharmacokinetic of LE showed a rapid, dose-dependent elimination with a total blood clearance (CLtotal) of higher than 60 ml/min/kg. The metabolism and excretion of LE also showed a marked dose-dependency. At 6 hr after iv of LE (0.5-10 mg/kg), the total recoveries (LE and the metabolites, AE & A, in bile and urine) were 99.35-26.72%. However, only about 2% of LE was excreted from the body through the urine. There were 0.93-2.12% and 0.66-0.26% of AE, and 75.67-19.69% and 20.74-2.77% of A excreted in the bile and urine, respectively. The excretion of A was dose dependent, and significantly higher at the lower dose. Using the (% of total excretion) vs. (log dose) plots, it could be predicted that almost all of the administered LE will be metabolized, and excreted as A when the systemic dose is lower than 0.25 mg/kg. CONCLUSIONS: The results indicate that LE absorbed systemically, after topical administration, can be rapidly transformed to the inactive metabolites, and eliminated from the body mainly through the bile and urine.

Androstadienes

[Prevalence of sleep apnea syndrome with primary arterial hypertension in a cardiologic rehabilitation clinic].

In a group of 132 randomly selected male patients with the admission diagnosis arterial hypertension in a cardiological rehabilitation clinic, nightly monitoring was performed with Mesam 4 with records of the metabolism laboratory values and sleep disturbances longitudinally. Desaturation indexes of > or = 10/h after manual correction for plausibility revealed a total prevalence of 27.3% in the case of breathing disturbances. The prevalence increased to 52% in the over 55 year-old patients with a Broca index of > or = 120% in comparison to merely 15.4% in standard weighted, comparable age group. No differences were found in the laboratory values. These results again show the frequent occurrence of the combination adiposity, hypertension, and sleep apnea syndrome which has often been missed previously in specialist rehabilitation clinics.

Adult

Role of the rac1 p21-GDP-dissociation inhibitor for rho heterodimer in the activation of the superoxide-forming NADPH oxidase of macrophages.

Activation of the superoxide (O2-)-generating NADPH oxidase of phagocytes requires the interaction of membrane-associated cytochrome b559 with three cytosolic components; p47-phox, p67-phox and sigma 1. We proposed that sigma 1 was a heterodimer composed of proteins of 22 kDa and 24 kDa that were tentatively identified as the small GTP-binding protein (G protein) rac1 p21 and GDP-dissociation inhibitor for rho (rho GDI). We now describe a modified procedure for the rapid purification of sigma 1 and demonstrate that the NADPH-oxidase-activating capacity is associated, throughout the purification sequence, with a protein binding 35S-labelled guanosine 5'-[3-O-thio]triphosphate. SDS/PAGE analysis confirmed the absolute association of sigma 1 activity with the presence of both the 22 kDa and 24 kDa proteins. Immunoblotting with a battery of antibodies against the small G proteins demonstrated that the 22-kDa protein was only recognized by antibodies reacting with rac1 p21; no reaction was found with anti-(rac2 p21), anti-[v-ras(H) p21] and anti anti-(rap1 p21). Free rac1 p21 (not in complex with rho GDI) was not detected at any stage of cytosol fractionation. The proteins comprising the sigma 1 heterodimer could be separated by reverse-phase chromatography and amino acid sequencing was performed on peptides derived by trypsin digestion of each of the isolated proteins. This demonstrated the identity of the 22-kDa protein with rac1 p21 and that of the 24-kDa protein with rho GDI. Purified heterodimeric sigma 1 did not require exogenous GTP for activity under conditions that assured the absence of free nucleotides. Treatment of the sigma 1 heterodimer with 1% sodium cholate, followed by gel filtration or anion-exchange chromatography in the presence of 1% sodium cholate, effectively separated rac1 p21 from rho GDI. Monomeric rac1 p21, obtained by these procedures, was able to stimulate cell-free O2- generation. Artificial heterodimeric sigma 1, capable of NADPH oxidase activation, could be reconstituted in vitro by recombining purified monomeric rac1 p21 and rho GDI and removing the sodium cholate used to dissociate the native sigma 1 dimer. Monomeric rac1 p21 exhibited an almost absolute dependence on exogenous GTP following removal of the endogenous nucleotide in low Mg2+ solution. Under similar conditions, heterodimeric sigma 1 was resistant to nucleotide exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence

D-dimer in the early diagnosis of thromboembolic disease in acute spinal injuries.

The role of monitoring plasma levels of D-dimer (XDP) as a diagnostic aid for thromboembolic disease was investigated in 267 patients admitted for acute care to the Prince Henry Hospital Spinal Unit. Elevated plasma XDP levels were found in 103 patients (39%) and a diagnosis of thromboembolic disease was made in 33. Thromboembolic disease was not found in patients whose XDP levels remained normal.

Acute Disease

Colonic volvulus in the spinal cord injured patient.

At the Prince Henry Hospital between 1970 and 1987, 8 cases of colonic volvulus were diagnosed in spinal cord injured (SCI) patients. This represents an incidence of 2.6% of SCI patients being treated at the hospital. The aetiology of volvulus is multifactorial and in these patients may be related to: neurological deficit; constipation as a result of immobility; and medications used for controlling muscle spasm, bladder and bowel function. Symptoms and signs are modified by the neurological deficit and awareness of the altered presentation will prevent delay and missed diagnoses. The effect of spinal cord injury and drugs on colonic motility needs further evaluation.

Aged

Community activism relating to a cluster of breast cancer.

In 1985, residents of a suburban community in South Florida became concerned when several young women were diagnosed with breast cancer. First as individuals, then through a community-based effort, they attempted to gain attention and action on what they believed to be a cluster of breast cancer. Through their efforts to find out whether some agent or toxic exposure existed in the community that might have caused breast cancer, the women formed a community-based organization. This paper describes the activism of the women to resolve the issue through an epidemiologic study of the breast cancer occurrence in their community. Furthermore, it substantiates the need and role of rational community response in resolving community threats and concerns.

Adult

Thermogenesis of white adipocytes: a novel method allowing long-term microcalorimetric investigations.

A microcalorimetric method was developed to facilitate long-term assessment of energy balance in isolated fat cells. White rat adipocytes were primary cultured in glass ampoules with a matrix of agar-gel. Heat production was measured continuously over 3 days with an LKB BioActivityMonitor. In order to assist interpretation of the microcalorimetric measurements, glucose consumption and lactate and pyruvate production were determined in parallel cultures. Heat production, glucose consumption and lactate production were in an apparent steady state throughout the study whether employing aerobic (94 pW, 0.50 and 0.44 pmol/cell. h, respectively) or partial anaerobic experimental conditions (39 pW, 0.41 and 0.57 pmol/cell.h, respectively). However, oxygen availability influenced the apparent heat production and glucose and lactate metabolism. With partial anaerobiosis a 59% lower heat production, an 18% lower glucose consumption and a 30% higher lactate production than by employing aerobic experimental conditions were observed.

Adipose Tissue