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Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 19 recordsLinked to original sources

DNA binds and activates complement via residues 14-26 of the human C1q A chain.

The mechanism by which DNA activates the classical complement pathway was investigated, with emphasis upon the C1q binding sites involved. DNA bound to both the collagen-like and globular regions of C1q. Binding reactivity with DNA was retained after reduction/alkylation and sodium dodecyl sulfate treatment of C1q. DNA bound preferentially to the A chain of C1q. Binding sites for DNA were localized by using synthetic C1q A chain peptides to two cationic regions within residues 14-26 and 76-92, respectively. Peptides 14-26 and 76-92 avidly bound DNA in enzyme-linked immunosorbent and gel shift assays. Peptide 14-26 also precipitated with DNA and blocked its ability to bind C1q and activate C. Replacement of the two prolines with alanines or scrambling the order of the amino acids resulted in loss of ability of peptide 14-26 to inhibit C1q binding and complement activation by DNA; similar investigations showed a sequence specificity for peptide 76-92 as well. These experiments identify C1q A chain residues 14-26 as the major site, and residues 76-92 as a secondary site, through which DNA binds C1q and activates the classical complement pathway, and demonstrate that a peptide identical to residues 14-26 can modulate C1q binding and complement activation by DNA.

Amino Acid Sequence

Percutaneous gastrostomy made simple.

The use of percutaneous endoscopic gastrostomy has obviated the necessity of laparotomy for enteral access. The authors propose a new technique for introduction of the gastrostomy tube. It entails use of the laparoscopic trocar to gain entrance into the gastric lumen.

Female

Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B.

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Dementia diseases and minor cognitive impairments in elderly patients in general practice. Results of a cross-sectional study].

General practitioners in 24 Mannheim practices kept a record of all over-65-year-old patients seen during four weeks (n = 3,737), and made ratings of their cognitive functioning with the help of simple guidelines. For a sub-sample of patients (n = 407), these ratings could be compared with assessments made by the research team, on the basis of a standardized interview and test procedure (Hierarchic Dementia Scale). The research data indicate that 8% of the patients manifested clinical dementia, a further 8% so-called 'mild dementia' and 17% milder, non-disabling degrees of cognitive impairment. The proportion of affected persons in each of the groups rises steeply with increasing age above 65 yr. The ability of the practitioners to detect dementia--including the milder degrees--among their elderly patients exceeded expectation (sensitivity 92%; specificity 76%). The test-score profiles of the patients, grouped according to their own doctors' ratings, conformed to clinical concepts of the progressive course ('staging') of dementing illness, while the degree of disability in everyday life, and dependency on others, also increased steeply across the groups. These findings emphasize the importance of general medical practice for the early detection of dementia in the elderly population, and potentially also for case management.

Activities of Daily Living

Risk factors for myocardial infarction after distal arterial reconstructive procedures.

This study identifies the preoperative, intraoperative, and postoperative factors associated with perioperative myocardial infarction (MI). The records of all patients who had distal vascular reconstructive procedures who sustained a perioperative MI were retrospectively reviewed from 1977 to 1990. From a total of 767 procedures, 18 (2.3%) patients suffered a MI. The mean time to MI after surgery was 1.8 days. Diabetes, heart murmur, and previous major amputations were identified as significant risk factors for the development of a perioperative MI. No laboratory or cardiographic data correlated with an increased risk, and the Goldman Index was inadequate in predicting perioperative MI risk.

Age Factors

Severe masseter myonecrosis in a horse.

A 6-year-old Quarter Horse was examined because of acute, severely swollen masseter muscles (palpation of which elicited pain response), exophthalmos, severe chemosis, and protrusion of the third eyelids. Blood selenium and vitamin E concentrations, and results of feed analysis and muscle biopsy supported a diagnosis of nutritional myopathy. The horse was treated and was clinically normal 2 weeks after discharge from the hospital.

Animals

Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy.

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.

Adenosine Triphosphate

Mental illness in a cross-national perspective. Results from a Brazilian and a German community survey among the elderly.

Findings for unselected samples for the elderly in two urban populations - one in Mannheim, Germany (n = 418) and the other in Sao Paulo, Brazil (n = 111) - are compared and contrasted. Each study was restricted to persons aged over 65 years living in private households, and each employed a single-stage method of psychiatric case-identification, based on the Clinical Interview Schedule (CIS). Apart from marked differences in educational standards and proportions living alone the two samples were broadly similar in their recorded socio-demographic characteristics. Comparison revealed no significant difference in total prevalence, though there was a trend towards a higher case-frequency in Sao Paulo (29.7%) than in Mannheim (23.3%). The clinical-item profiles for the two samples indicated a higher rate of symptom reporting in Sao Paulo, whereas the Mannheim sample had higher mean scores for a number of psychiatric abnormalities observed at interview. Separate cluster analyses carried out on the two data sets divided the samples into four pairs of sub-groups with similar clinical profiles, which were designated respectively as 'organic', 'depressive', 'neurotic' and 'normal'. While a more careful standardization of method would probably reduce the observed disparities between the samples, some of these are thought to be real and to relate to sociocultural differences, as well as to the greater stresses of daily life in Sao Paulo.

Aged

The epidemiology of primary degenerative dementia and related neurological disorders.

Observation of cytopathological similarities between the changes of Alzheimer-type dementia, Parkinson's disease and motor neuron disease, as well as of some degree of clinical association between these conditions, has led to the suggestion that all three belong to a common class of degenerative neurological disorders, each of which as a rule first becomes manifest when age-related neuronal attrition is superimposed on subclinical damage caused by environmental noxae earlier in life. The importance of this model lies in its potential relevance to prevention. The epidemiological data reviewed here suggest that, while the three disease groups are all strongly linked with ageing, there may be major differences between their patterns of occurrence in populations, which make it doubtful if the same environmental pathogens are responsible in each instance. The most plausible unifying hypothesis at present is that the predisposing neuronal damage can be caused by a number of widely distributed metallic neurotoxins, each of which has a tendency to pick out specific areas or cell groups within the CNS and thus to give rise to distinct though overlapping clinical syndromes. The evidence bearing on this and other causal hypotheses is, however, still tenuous because of the scarcity of empirical data. Population-based case-control and cohort studies are called for, as part of a co-ordinated research endeavour.

Aged

Panniculitis in an immunocompromised patient.

We present a patient in whom histoplasmosis panniculitis developed during steroid therapy for pancytopenia secondary to myelodysplasia. Although the cutaneous manifestations of disseminated histoplasmosis are rare, we review them because of the increasing numbers of organ-transplant patients, as well as other patients with immunodeficiency, including acquired immune deficiency syndrome, in whom the risk of this unusual presentation of histoplasmosis must be considered.

Aged

Study of the definition of nosocomial infections (SDNI). Research Committee of the Association for Practitioners in Infection Control.

If nosocomial infections are to be used as clinical indicators of quality, their definitions must be accurate. To assess validity and reliability of definitions of nosocomial infection, a study was conducted in two groups of U.S. hospitals. Group A consisted of a stratified, random sample of 715 hospitals and excluded those that are part of the National Nosocomial Infections Surveillance System. The 112 NNIS hospitals were surveyed separately in group B. Both groups used the same instrument, consisting of 36 case studies simulating patients' charts. Content and construct validity were formally tested and demonstrated. Six case studies were presented for each of the four major NI sites and for community-acquired or no infection. The pooled hospital response was 48% (396/827). The pooled number of individual responders whose data were used in the analysis was 469. Their overall mean score was 84%, and the score for correctly identifying any NI was 83%. Both groups were best at identifying urinary nosocomial infections (Group A = 92%, Group B = 93%) and poorest for no infection (Group A = 62%, Group B = 75%). Group A responders had significantly higher scores if they were certified, had a baccalaureate or higher degree, had taken a formal infection control course, had worked in infection control for greater than or equal to 2 years, or had worked full time in infection control in a greater than or equal to 200-bed hospital that was affiliated with a medical school (all p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Centers for Disease Control and Prevention, U.S.

Stroke rehabilitation: Australian patient profile and functional outcome.

A prospective, multi-institutional, population based study identified 1274 non-surgical stroke admissions to all hospitals in a major Australian city during 1984. The demographic and diagnostic profile and the nature of functional recovery of all 258 first stroke survivors who were referred for inpatient rehabilitation are presented. The median duration of rehabilitation stay was 49 days. The mean functional independence score, as measured on a modified Barthel Index at admission was 44, compared with 78 on discharge, a mean improvement of 34. Stair climbing had the lowest mean value on admission (12), while bowel control had the lowest residual deficit on discharge (95). The stroke study group was representative of the unimpaired aged population in all respects except ethnicity, where differences are attributed to age. The variables identified as significant are; side and severity of paralysis, age and sex, marital status and ethnicity. Stroke rehabilitation outcome was not influenced by etiology, site of lesion, arterial distribution, occupation or education.

Activities of Daily Living

The prevalence of dementia in Europe: a collaborative study of 1980-1990 findings. Eurodem Prevalence Research Group.

To obtain age- and gender-specific estimates of the prevalence of dementia in Europe and to study differences in prevalence across countries, we pooled and re-analysed original data of prevalence studies of dementia carried out in some European countries between 1980 and 1990. The study followed these steps: census of existing datasets, collection of data in a standardized format, selection of datasets suitable for comparison, comparison of age and gender patterns. From the 23 datasets of European surveys considered, 12 were selected for comparison. Only population-based studies in which dementia was defined by DSM-III or equivalent criteria and in which all subjects were examined personally were included. Studies in which institutionalized subjects were not investigated were excluded. Age- and gender-specific prevalences were compared within and across studies and overall prevalences were computed. Although prevalence estimates differed across studies, the general age- and gender-distribution was similar for all studies. The overall European prevalences for the five-year age groups from 60 to 94 years, were 1.0, 1.4, 4.1, 5.7, 13.0, 21.6 and 32.2%, respectively. In subjects under 75 years the prevalence of dementia was slightly higher in men than in women; in those aged 75 years or over the prevalence was higher in women. The prevalence figures nearly doubled with every five years of increase in age.

Adult

Properties of high-threshold mechanoreceptors in the oral mucosa. I. Responses to dynamic and static pressure.

1. Mechanical response properties of high-threshold mechanoreceptors (HTMs) of the goat oral mucosa were determined by single-unit recording from the palatine and alveolar nerves and from the trigeminal ganglion. The following observations were made. 2. HTMs of the oral mucosa could be separated into two subgroups on the basis of their threshold to mechanical stimulation. Intense pressure receptors (IPRs) comprised a group of A-delta afferents with thresholds of 2-16 g. Mechanonociceptors (MNs) comprised a group of relatively slowly conducting afferents (A-delta and C-fibers) with a higher threshold range (16-300 g). 3. In most instances, MNs lacked pressure-transducing capacity. Tests of reactivity to dynamically or statically applied stimuli revealed that significant functions were rarely fit between MN activity and pressure (4/20 cases). 4. IPRs differed from MNs by their pressure-transducing properties. The afferent response interval was in inverse proportion to the applied pressure. Significant pressure interval functions were fit in 16/20 cases. The relationship between pressure and response interval was best described by power functions. 5. Tests of reactivity to dynamically or statically applied stimuli revealed that IPRs preferred static pressure. Tighter fits and steeper slopes were observed in power functions fit to data generated by statically applied stimuli (mean fitted function, dynamic test: LnISI = -0.97 LnP + 3.4; mean fitted function, static test: LnISI = -1.6 LnP + 4.71). 6. Pressures-frequency thresholds (PFTs), asymptotes (PFAs), and mean response intervals (MRIs) were determined for IPRs from the static test series. The first two values are the pressures that produce the lower and upper limits of response frequency of mucosal HTMs (mean PFT, 1.48 N/mm2; mean PFA, 3.34 N/mm2). The MRI (28 ms) is simply computed from the function. When PFTs and PFAs are combined with activation threshold and power functions, they provide a relatively complete description of the range and form of reactivity of the IPR of the oral mucosa.

Animals

Properties of high-threshold mechanoreceptors in the goat oral mucosa. II. Dynamic and static reactivity in carrageenan-inflamed mucosa.

1. We have previously described two classes of high-threshold mechanoreceptors (HTMs) of the oral mucosa of the goat. Mechanonociceptors (MNs) had very high thresholds (16-300 g) and were poor transducers of pressure. Intense pressure receptors (IPRs) had thresholds from 2 to 16 g and were good transducers of pressure. After carrageenan inflammation (CI) we observed mechanical sensitization in both classes of HTMs. The characteristics were as follows. 2. Sensitization of MNs was manifested as qualitative shifts in the capacity to encode intense pressure. MNs that were unable to code intensity before CI acquired pressure coding properties after treatment with carrageenan. Qualitative shifts in coding capacity were suggested by the greater proportion of MNs coding in preinflamed (10 of 14) compared with noninflamed tissue (8 of 25 cases). Improved afferent reactivity was directly observed, in additional experiments, in which MNs were characterized in normal tissue before the injection of carrageenan into the mucosa. In five of six cases, either qualitative or quantitative improvements were observed. In control experiments, improved reactivity was observed in one of six cases. 3. Sensitization in IPRs was manifested as both qualitative and quantitative improvement in intensity coding properties. Power functions fit to individual IPRs indicated sensitization for most mucosal afferents after inflammation. Carrageenan induced decreases in the mean response interval, pressure-frequency threshold (PFT), and pressure-frequency asymptote (PFA), and decreases in variability of functions fit to units sampled from preinflamed and noninflamed tissue (n = 23). Experiments were also conducted in which units were characterized before and after carrageenan treatment. In 7 of 10 cases, injection of carrageenan into the oral mucosal led to improved dynamic and/or static reactivity. Injection of vehicle led to changes in reactivity in one of five cases. 4. Carrageenan induced decreases in activation thresholds only when afferent receptive fields fell into restricted tissue zones. Large shifts in activation thresholds were observed for five of five (3 MNs and 2 IPRs) units in the sulcal zone of the incisal papilla (IP). In contrast, activation thresholds increased or remained the same in 11 of 12 units (10 IPRs and 3 MNs) with receptive fields in the medial or ventral tissue zones. Changes in activation threshold evolved slowly after carrageenan injection and required 1-2 h to develop. Rapid changes in activation threshold were also observed in a limited number of cases (3). These threshold shifts were unrelated to carrageenan inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals