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Biomedical subjects

R M Palmer

Publications and source records attributed to R M Palmer.

At least 19 recordsLinked to original sources

Characteristics and outcomes of patients who self-extubate from ventilatory support: a case-control study.

OBJECTIVE: To identify factors associated with the occurrence of deliberate self-extubation and to describe associated patient outcomes. DESIGN: Case-control study. SETTING: ICUs of a national referral, tertiary medical center. PARTICIPANTS: Fifty adult, intubated patients who had self-extubated from mechanical ventilatory support. Two control subjects who had not self-extubated were matched to each case based on age, gender, primary discharge diagnosis, and time hospitalized (within same quarter). MEASUREMENTS: Standardized coding of medical record information, including demographic characteristics, clinical information, intubation and mechanical ventilation characteristics, medications, and selected laboratory indexes. RESULTS: As compared to the control subjects, patients who self-extubated were more likely to be medical than surgical patients (p<0.001) and have a current history of smoking (p<0.05). Prior to the self-extubation, patients had a greater likelihood of hospital-acquired infections (p<0.001) or other hospital-acquired adverse events (p<0.001), abnormal (<10, >50 mg/dL) BUN (p<0.05), and abnormal (<20, >50 mm Hg) PaCO2 (p<0.05); they also were more likely to be restless or agitated (p<0.001), and more likely to be physically restrained (p<0.001). A logistic regression model demonstrated that presence of restlessness or agitation and presence of a hospital-acquired adverse event were independently associated with self-extubation from mechanical ventilatory support. In examining outcomes, as compared to the control subjects, those who self-extubated had longer lengths of stay in ICU and hospital, were more likely to need reintubation, and were more likely to suffer complications from intubation. However, none of the cases died within 48 h of self-extubation. CONCLUSION: The results underscore the need for clinical guidelines for weaning and for monitoring patients at risk of self-extubation.

Adult

Paraneoplastic cerebellar degeneration. Case report and literature review.

Paraneoplastic cerebellar degeneration (PCD) presents with acute or subacute onset of ataxia, dysarthria, and intention tremor. In patients older than 50 years, acute or subacute cerebellar degeneration is paraneoplastic in origin in 50% of cases. Paraneoplastic cerebellar degeneration most often precedes a potentially curable remote malignancy. Less often, PCD occurs in a patient with a known malignancy or heralds the onset of a recurrence. The presence of specific antibodies in serum samples helps to guide identification of the occult underlying malignancy. Physicians should entertain the diagnosis of PCD when older patients present with signs of cerebellar degeneration without an obvious cause. A systematic evaluation, including the selection of appropriate imaging and laboratory studies, will often enable physicians to identify the responsible cancer. However, because PCD can precede a cancer by months to years, periodic reevaluation is needed when the cancer remains occult.

Adenocarcinoma

The role of the dental team in the promotion of smoking cessation.

Dentists and their support staff are in an ideal position to help patients cut down or stop smoking. In this paper Professor Palmer and Dr Newton review the literature on the promotion of smoking cessation in dental settings so that members of the dental team will feel more confident about helping and assisting patients to reduce their smoking habits.

Attitude of Health Personnel

Regulation of phospholipase D in L6 skeletal muscle myoblasts. Role of protein kinase c and relationship to protein synthesis.

The addition of vasopressin or 12-O-tetradecanoylphorbol-13-acetate (TPA) to prelabeled L6 myoblasts elicited increases in [14C]ethanolamine release, suggesting the activation of phospholipase D activity or activities. While the effects of both agonists on intracellular release were rapid and transient, when extracellular release of [14C]ethanolamine was measured, the effect of vasopressin was again rapid and transient, whereas that of TPA was delayed but sustained. Effects of both agonists on intra- and extracellular release were inhibited by the protein kinase C (PKC) inhibitor, Ro-31-8220, and PKC down-regulation by preincubation with TPA. The formation of phosphatidylbutanol elicited by vasopressin and TPA mirrored their effects on extracellular [14C]ethanolamine release in that the former was transient, whereas the latter was sustained. Responses to both agonists were abolished by PKC down-regulation. When protein synthesis was examined, the stimulation of translation by TPA and transcription by vasopressin were inhibited by Ro-31-8220. In contrast, down-regulation of PKC inhibited the synthesis response to TPA but not vasopressin. Furthermore, following down-regulation, the effect of vasopressin was still blocked by the PKC inhibitors, Ro-31-8220 and bisindolylmaleimide. Analysis of PKC isoforms in L6 cells showed the presence of alpha, epsilon, delta, mu, iota, and zeta. Down-regulation removed both cytosolic (alpha) and membrane-bound (epsilon and delta) isoforms. Thus, the elevation of phospholipase D activity or activities induced by both TPA and vasopressin and the stimulation of translation by TPA involves PKC-alpha, -epsilon, and/or -delta. In contrast, the increase in transcription elicited by vasopressin involves mu, iota, and/or zeta. Hence, although phospholipase D may be linked to increases in translation elicited by TPA, it is not involved in the stimulation of transcription by vasopressin.

Analysis of Variance

Relation between symptoms of depression and health status outcomes in acutely ill hospitalized older persons.

BACKGROUND: Older patients often have poor health status outcomes after hospitalization. Symptoms of depression are common in hospitalized older persons and may be a risk factor for these poor outcomes. OBJECTIVE: To determine whether symptoms of depression predict worse health status outcomes in acutely ill, older medical patients, independent of health status and severity of illness at hospital admission. DESIGN: Prospective cohort study. SETTING: Medical service of a teaching hospital. PATIENTS: 572 hospitalized medical patients older than 70 years of age. MEASUREMENTS: 15 symptoms of depression, health status, and severity of illness were measured at admission. The main outcome was dependence in basic activities of daily living at discharge and 30 and 90 days after discharge. Other outcome measures were dependence in instrumental activities of daily living, fair or poor global health status, and poor global satisfaction with life. RESULTS: The median number of symptoms of depression on admission was 4. Patients with 6 or more symptoms on admission (n = 196) were more likely than patients with 0 to 2 symptoms (n = 181) to be dependent in basic activities of daily living (odds ratio, 2.47 [95% CI, 1.58 to 3.86]) after controlling for demographic characteristics and severity of illness. At each subsequent time point, patients with more symptoms of depression on admission were more likely to be dependent in basic activities of daily living. This association persisted after adjustment for dependence in basic activities of daily living, severity of illness, and demographic characteristics on admission. The odds ratios comparing patients who had 6 or more symptoms with those who had 0 to 2 symptoms were 3.23 (CI, 1.76 to 5.95) at discharge, 3.45 (CI, 1.81 to 6.60) 30 days after discharge, and 2.15 (CI, 1.15 to 4.03) 90 days after discharge. At each time point, patients with 6 or more symptoms of depression were more likely to have more dependence in instrumental activities of daily living, worse global health status, and less satisfaction with life. CONCLUSIONS: Symptoms of depression identified a vulnerable group of hospitalized older persons. The health status of patients with more symptoms of depression was more likely to deteriorate and less likely to improve during and after hospitalization. This association was not attributable to health status or severity of illness on admission. The temporal sequence and magnitude of this association, its consistency over time with different measures, and its independence from the severity of the somatic illness strongly support a relation between symptoms of depression on admission and subsequent health status outcomes.

APACHE

Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells: effect of differentiation and fusion.

In proliferating C2C12 myoblasts, serum and physiological concentrations of insulin and IGF-I stimulated protein synthesis and RNA accretion. After fusion, the multinucleated myotubes remained responsive to serum but not to insulin or IGF-I, even though both insulin and type-I IGF receptor mRNAs increased in abundance. Protein synthetic responses to insulin and IGF-I in myoblasts were not inhibited by dexamethasone, ibuprofen or Ro-31-8220, thus phospholipase A2, cyclo-oxygenase and protein kinase C did not appear to be involved in the signalling mechanisms. Neither apparently were polyphosphoinositide-specific phospholipase C or phospholipase D since neither hormone increased inositol phosphate, phosphatidic acid, choline or phosphatidylbutanol production. Only the phosphatidylinositol-3-kinase inhibitor, wortmannin, and the 70 kDa S6-kinase inhibitor, rapamycin, wholly or partially blocked the effects of insulin and IGF-I on protein synthesis. 2-deoxyglucose uptake remained responsive to insulin and IGF-I after fusion and was also inhibited by wortmannin. The results suggest that the loss of responsiveness after fusion is not due to loss of receptors, but to the uncoupling of a post-receptor pathway, occurring after the divergence of the glucose transport and protein synthesis signalling systems, and that, if wortmannin acts at a single site, this is prior to that point of divergence.

Animals

Measuring prognosis and case mix in hospitalized elders. The importance of functional status.

OBJECTIVE: Although physical function is believed to be an important predictor of outcomes in older people, it has seldom been used to adjust for prognosis or case mix in evaluating mortality rates or resource use. The goal of this study was to determine whether patients' activity of daily living (ADL) function on admission provided information useful in adjusting for prognosis and case mix after accounting for routine physiologic measures and comorbid diagnoses. SETTING: The general medical service of a teaching hospital. PARTICIPANTS: Medical inpatients (n = 823) over age 70 (mean age 80.7, 68% women). MEASUREMENTS: Independence in ADL function on admission was assessed by interviewing each patient's primary nurse. We determined the APACHE II Acute Physiology Score (APS) and the Charlson comorbidity score from chart review. Outcome measures were hospital and 1-year mortality, nursing home use in the 90 days following discharge, and cost of hospitalization. Patients were divided into four quartiles according to the number of ADLs in which they were dependent. MAIN RESULTS: ADL category stratified patients into groups that were at markedly different risks of mortality and higher resource use. For example, hospital mortality varied from 0.9% in patients dependent in no ADL on admission, to 17.4% in patients dependent in all ADLs. One-year mortality ranged from 17.5% to 54.9%, nursing home use from 3% to 33%, and hospital costs varied by 53%. In multivariate analyses controlling for APS. Charlson scores, and demographic characteristics, compared with patients dependent in no ADL, patients dependent in all ADLs were at greater risk of hospital mortality (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.1-58.8), 1-year mortality (OR 4.4; 2.7-7.4), and 90-day nursing home use (OR 14.9; 6.0-37.0). The DRG-adjusted hospital cost was 50% higher for patients dependent in all ADLs. ADL function also improved the discrimination of hospital and 1-year mortality models that considered APS, or Charlson scores, or both. CONCLUSIONS: ADL function contains important information about prognosis and case mix beyond that provided by routine physiologic data and comorbidities in hospitalized elders. Prognostic and case-mix adjustment methods may be improved if they include measures of function, as well as routine physiologic measures and comorbidity.

Activities of Daily Living

A randomized controlled trial of a 2% minocycline gel as an adjunct to non-surgical periodontal treatment, using a design with multiple matching criteria.

Topical locally delivered minocycline is an adjunctive to non-surgical periodontal treatment, but there are few reported trials. Previous trials have reported differences between changes in probing depth in treatment and control groups, but no differences in probing attachment level. In the present study, 30 subjects were paired according to gender, age, ethnic group, smoking habits, and probing depths. Both groups received intensive oral hygiene education and root planing with local anaesthesia. Active or placebo gel was placed subgingivally at planed sites in each subject according to a double-blind protocol, immediately after instrumentation, and 2 and 4 weeks later. A periodontal examination was made with a constant force probe before instrumentation, and 6 and 12 weeks later, 2 subjects failed to complete the study, and their pairs were therefore not included in the analysis. Results were tested with analysis of covariance. Differences between groups in mean probing depth did not reach statistical significance at any visit (baseline: test (T) = 5.93 mm, control (C) = 5.74 mm; 6 weeks: T = 3.53 mm, C = 3.63 mm; 12 weeks: T = 3.29 mm, C = 3.44 mm), but mean probing attachment levels were different (p < 0.05) at both reassessments (baseline: T = 6.86 mm, C = 6.83 mm; 6 weeks: T = 4.93 mm, C = 5.30 mm; 12 weeks T = 4.91 mm, C = 5.27 mm). There was also a difference in the number of sites with bleeding on deep probing at 12 weeks (p < 0.05). This trial showed that adjunctive minocycline gel provided a more advantageous outcome for nonsurgical periodontal treatment in terms of probing attachment level and bleeding on deep probing. This trial was a good example of experimental, as opposed to community, design, and used limited resources to show a clear result.

Administration, Topical

Cytokeratin phenotypes at the dento-gingival junction in relative health and inflammation, in smokers and nonsmokers.

OBJECTIVES: The cells of the junctional epithelium (JE) provide and maintain the epithelial attachment, and remain morphologically and phenotypically distinct from oral sulcular (OSE) and external oral epithelia (EOE), from which they may be regenerated de novo. Expression of cytokeratins (CK) in human epithelia has been shown to be highly site-specific, implying a functional role. The aims of this study were to differentiate between the cytokeratin profiles of JE, OSE, EOE and pocket epithelia (PE) in health and disease, in smokers and non-smokers. MATERIALS AND METHODS: The cytokeratin profiles of 40 samples of healthy and clinically inflamed human gingival tissue taken from 15 smokers and 25 non-smokers were studied by immunocytochemistry. Cryostat sections of fresh frozen gingival tissues were stained with a panel of monoclonal antibodies (mAb) and visualised by a biotin-Streptavidin-peroxidase complex technique. RESULTS: JE and PE expressed an identical range of cytokeratins irrespective of the inflammatory or smoking status, with the exception of CK4 expression, which tended to be increased in smokers. The OSE and EOE expressed non-cornifying and cornifying differentiation cytokeratins respectively, but in the presence of inflammation, both these epithelia showed increased expression of CK19 at a basal level in association with expression of one or more of the simple cytokeratins. JE/PE expressed CK17 in external layers only, approximating the tooth surface. All epithelia expressed CK6, 16 the markers of high cell turnover. CONCLUSIONS: CK 19 was a consistent differentiation marker for JE and PE. Expression of CK8, 18 was enhanced by inflammation. CK4 expression increased in association with smoking. Markers of differentiation were not always co-expressed equally within a pair. Pairs were not always completely mutually exclusive with frequent co-localisation.

Adolescent

When your patient is hospitalized: tips for primary care physicians.

Outcomes of hospitalization of elderly patients can be improved through a systematic and comprehensive approach that physicians can incorporate into their practices. The first step is to recognize the patients who are at risk for functional decline in hospital, despite appropriate treatment of their acute illness. Many of these patients will present with one or more of the common geriatric syndromes, functional dependency, cognitive dysfunction (delirium), mood disorders (depression), and malnutrition. The next step is to avoid iatrogenic illness from diagnostic tests or medications and deconditioning due to immobility. Finally, discharge planning can help to ensure that patients receive needed services when they leave the hospital.

Activities of Daily Living

Cyclic AMP stimulates protein synthesis in L6 myoblasts and its effects are additive to those of insulin, vasopressin and 12-0-tetradecanoylphorbol-13-acetate. Possible involvement of mitogen activated protein kinase.

The role of cyclic AMP as a second messenger in the stimulation of protein synthesis and the potential involvement of mitogen activated protein (MAP) kinase in this response was studied in L6 myoblasts. Dibutyryl-cAMP (dbt-cAMP) increased protein synthesis at 90 min and 6 h in a concentration-dependent manner. The responses at 90 min were probably mediated by increased translation as they were not blocked by actinomycin D; effects at 6 h were accompanied by increases in RNA content implying a transcriptional component. 100 nM 12-0-tetradecanoylphorbol-13-acetate (TPA), 1 nM Insulin (90 min incubations) and 100 nM vasopressin (6 h incubation) also increased protein synthesis and these responses were additive with those of 500 micron dbt-cAMP. Responses to forskolin were similar to dbt-cAMP whilst 1,9-dideoxyforskolin had no effect. Cell extracts immunoblotted with MAP kinase antibody showed bands corresponding to approx. 42, 44, 54 and 83 kDa. 500 micron dbt-cAMP elicited an increase in activity of both the 42 and 44 kDa bands when assayed by the 'in gel' method and a similar response was also observed with forskolin. TPA and vasopressin also stimulated the activity of these two isoforms, but had no significant additive or inhibitory effects when added in combination with 500 micron dbt-cAMP. In contrast, although 1 nM insulin alone had no effect, a synergistic response in terms of MAP kinase activation was observed in the presence of dbt-cAMP. The data demonstrate that cAMP stimulates protein synthesis in L6 cells and suggest a role for MAP kinase in this event.

Animals

Measurement of protein degradation by release of labelled 3-methylhistidine from skeletal muscle and non-muscle cells.

The rates of [3H]N(tau)-methylhistidine (3-MH) accumulation in the medium, following pulse labelling of cells for 48 h with [3H]methionine, were used to measure myofibrillar protein degradation. In fused C2C12 myotubes, incubation for 24 or 48 h after the labelling period gave rates of myofibrillar degradation of 38 and 42%/day. In a leucine free medium, these rates were similar; 40 and 47%/day, respectively. Using identical conditions +/- leucine, but in the absence of [3H]-methionine, rates of protein accretion and synthesis over 24-48 h were measured. From these data, rates of total protein degradation were calculated by difference and were similar to myofibrillar degradation rates. We have used the same pulse labelling protocol to assess whether the method is applicable to non-muscle cell lines based on the knowledge that 3T3 fibroblasts contain actin in the cytoskeleton. 3-MH was detected both in protein and upon its release into the medium. Actin degradation measured over a 48 h period gave a value half that obtained for total degradation, but the results suggest that the release of 3-MH by fibroblasts in vivo could be appreciable. The development of this methodology should provide a useful tool to investigate signalling mechanisms regulating actin degradation in a variety of cell types.

3T3 Cells

Development and cell fate in interspecific (Mus musculus/Mus caroli) intraocular transplants of mouse molar tooth-germ tissues detected by in situ hybridization.

Mandibular first molar tooth germs were dissected from Mus musculus (CDI) and Mus caroli (age range: 14-day embryo to 1-day postnatal). Most of the tooth germs were separated enzymically into epithelial and mesenchymal components. Interspecific tissue recombinations and intact M. caroli tooth germs were grown in the anterior chamber of the eye of adult CDI mice for 24 weeks. Recombinations of M. caroli enamel-organ epithelium with M. musculus, dental papilla and follicle mesenchyme developed into normal teeth with advanced root, periodontal ligament and bone formation, thereby confirming extensive epithelial-mesenchymal interactions across the species barrier. Labelling sections by in situ hybridization with a M. musculus-specific DNA probe (pMSat5) showed that almost all cells in the pulp, periodontal ligament and bone were M. musculus, including cementoblasts. Reduced enamel epithelium and epithelial cell rests derived from donor M. caroli enamel organ were unlabelled. This indicates that any cementogenic role of Hertwig's epithelial root sheath must be short-lived. The immunological privilege of the intraocular transplantation site in M. musculus CDI mice did not extend to grafts including xenogeneic M. caroli dental mesenchyme. Thus, intact M. caroli tooth germs and recombinations of M. musculus enamel organ with M. caroli dental papilla and follicle showed limited development, with no root formation, and were populated almost exclusively with labelled host M. musculus lymphocytes.

Alveolar Process

A double-blind trial of tetracycline in the management of early onset periodontitis.

The aim of the study was to evaluate the adjunctive effect of systemic tetracycline (250 mg qds for 14 days) in sequential root planing and surgical phases of treatment in a randomised, double-blind controlled trial. 38 patients who were under 26 years of age, in good general health and with localised (15 test/15 control) or generalised (4 test/4 control) early onset periodontitis completed the non-surgical phase. Data were analysed by ANOVA using baseline covariates and transformations where appropriate. Improvements in probing depth, probing attachment level and bleeding on probing were significantly better in the group treated with adjunctive tetracycline, at 3 months post-treatment. 26 patients (13 test/13 control) subsequently completed the surgical phase (modified Widman flap surgery with adjunctive tetracycline or placebo as before) and were re-examined at 6 months and 12 months. In the test group, 58% of the originally affected teeth required surgery compared to 75% in the control group. Surgery produced further reductions in mean probing depths but no further gains in probing attachment. There were no further statistically significant differences between test and control groups for any of the clinical measures, although the tetracycline group appeared to maintain an advantage. In conclusion, systemically administered tetracycline is a useful adjunct in the management of early onset periodontitis, particularly in non-surgical treatment.

Administration, Oral

N tau-methylhistidine turnover in skeletal muscle cells measured by GC-MS.

A method that employs gas chromatography-mass spectrometry has been developed to measure N tau-methylhistidine (3-methylhistidine; 3-MH) synthesis and release from skeletal muscle myotubes in vitro. It shows excellent linearity (0.9999) over the range studied (0-4 nmol), high recovery (92.6%), and low coefficient of variation (1.6%). 3-MH release from myotubes was essentially linear over a 96-h incubation, whereas the loss of 3-MH from cell protein accelerated with increasing time, an effect due, at lest in part, to decreasing rates of total protein synthesis. When incubated in either glutamine-free or methionine-free medium for 48 h, 3-MH in cell protein and appearing in the medium were greatly reduced compared with the 48-h controls, suggesting that hypertrophy was greatly reduced. Similar but lesser trends were observed with adenosine 3',5' -cyclic monophosphate. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) appeared to both stimulate 3-MII synthesis and inhibit its release during a 48-h incubation. The development of this method facilitates detailed investigation into the mechanisms through which agents such as TPA regulate myofibrillar protein degradation.

Bucladesine

Repartitioning of maternal muscle protein towards the foetus induced by a polyclonal antiserum to rat GH.

Growth and protein accretion were studied in maternal muscle and liver and in foetuses of rats on day 20 of pregnancy. In young rats, weighing 120 g at mating, muscle mass and protein content of three hind-limb muscles, soleus, plantaris and gastrocnemius, increased on average by 7% compared with non-pregnant controls although the rate of muscle protein synthesis was decreased. In mature rats, rates of muscle protein synthesis were also reduced on day 20 of pregnancy but no change in muscle mass was observed. Rates of liver protein synthesis and accretion were increased in the pregnant animals; the effect was larger in the young pregnant rat. Administration of an antibody to rat GH (anti-rGH) for 10 days to young pregnant rats reversed the effect on the same three maternal muscles and resulted in a 9-11% lower muscle mass and protein content, compared with control pregnant animals. In both young and mature dams serum IGF-I concentrations were halved on day 20 of pregnancy, a further small reduction was observed in response to anti-rGH. No significant change in serum insulin or corticosterone levels was observed. Anti-rGH treatment also reduced food intake but foetal weight at 20 days was significantly increased (14%). The effects on maternal muscle were not the result of loss of appetite associated with anti-GH administration as, in rats pair-fed to the intake of the anti-rGH group, maternal muscle and foetal weights were the same as in animals with food available ad libitum. The data suggest that the GH/IGF axis is involved in the partitioning of nutrients between the dam and the foetus.

Animals