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Biomedical subjects

P Douglas

Publications and source records attributed to P Douglas.

At least 37 records · Page 2Linked to original sources
PubMed1996

Restrictive left ventricular filling patterns in very old patients with congestive heart failure: clinical correlates and prognostic significance.

OBJECTIVES: In certain younger patients with congestive heart failure (CHF), Doppler/echocardiography has identified a "restrictive" pattern of early diastolic ventricular filling characterized by very rapid early filling and a steep deceleration slope. We asked whether a similar restrictive pattern can be identified in very old patients with CHF, and if so, what are its clinical correlates and prognostic implications. DESIGN: Retrospective cohort with prospective follow-up. SETTING: Academic long-term care facility. PARTICIPANTS: Thirty-nine residents with clinical CHF (age 89 +/- 5 (SD) years) MEASUREMENTS: Transmitral Doppler flow, clinical characteristics, recurrent CHF episodes, hospitalizations, and mortality were measured. RESULTS: Fifteen (38%) of the subjects had restrictive filling patterns, characterized by a ratio of early to late flow (E/A) > 1.00 and 24 (62%) had nonrestrictive patterns. The restrictive pattern was associated with a longer duration of CHF, more angina, and higher rate of symptomatic recurrences of CHF. CONCLUSION: A restrictive diastolic filling pattern may represent a late stage in the evolution of congestive heart failure when left ventricular filling pressure is markedly increased. The treatment of CHF in older patients may need to account for different patterns of diastolic filling.

Age Factors↗
PubMed1996

Reciprocal influences among adrenocortical activation, psychosocial processes, and the behavioral adjustment of clinic-referred children.

The reciprocal effects among cognitive-behavioral, environmental, and biological influences on clinic-referred children's (N = 64; 34 boys; M age 12.71 years) short-term psychological and psychiatric adjustment were studied. At clinic intake and 6 months later, standardized measures of adjustment and control-related beliefs were assessed. Before and after conflict-oriented parent-child interaction tasks the children's saliva was sampled. Adrenocortical responses (i.e., increases in salivary cortisol) to the social conflict task predicted children's internalizing problem behaviors and anxiety disorders at follow-up. Consistently high adrenocortical reactivity at intake and follow-up was associated with deflated social competence over the 6-month period. Also, specific patterns of discontinuity in children's internalizing behavior problems predicted individual differences in their subsequent adrenocortical responsiveness. Specifically, rising behavior problem levels across time predicted higher and declining behavior problem levels predicted lower adrenocortical reactivity at follow-up. Findings are among the first to suggest links among internalizing behavior problems, adrenocortical responsiveness to social challenge, and clinic-referred children's short-term cognitive-behavioral and emotional adjustment.

Adolescent↗
PubMed1995

Identification of a regulatory phosphorylation site in the hinge 1 region of nitrate reductase from spinach (Spinacea oleracea) leaves.

Purified nitrate reductase (NR) from spinach leaves was phosphorylated in vitro by NR-inactivating kinase on Ser-543 which is located in the hinge 1 region between the molybdenum-cofactor and haem-binding domains. Phosphorylation of Ser-543 allowed NR to be inhibited by the inhibitor, NIP. Degraded NR preparations in which a proportion of the subunits had lost 45 amino acids from the N-terminus during purification could be phosphorylated by NR kinase on Ser-543, but could not subsequently be fully inhibited by NIP, suggesting a role for the N-terminal tail of NR in NIP binding.

Amino Acid Sequence↗
PubMed1994

Polarized distribution of the trans-Golgi network marker TGN38 during the in vitro development of neocortical neurons: effects of nocodazole and brefeldin A.

Neurons are polarized secretory cells whose cytoplasm and plasma membrane are polarized to form two compartments: dendrites and axons. In mature, fully polarized neurons, the microtubule-associated protein Map2 is targeted to dendrites, while tau is mainly restricted to axons. However, the intraneuronal distribution of secretory pathway organelles, such as the endoplasmic reticulum and the Golgi complex, which give rise to all constitutive, regulated and lysosome vesicles, is poorly understood. Thus, to investigate the distribution of the trans-Golgi network during the development and maturation of rat neocortical neurons in vitro, we have utilized an antibody recognizing a 38 kDa trans-Golgi network-specific protein, TGN38, and immunofluorescence microscopy. Before neurons have established polarity. TGN38 immunoreactivity outlines several vesicles dispersed throughout the cell body cytoplasm; these converge close to a major Map2-immunopositive process during the establishment of neuronal polarity, and later merge into a single structure located at the base of a thick Map2-immunopositive process, approximately 18 h after plating. At this stage TGN38 immunoreactivity is located within 45 degrees of the major Map2-immunoreactive process in 54% of neurons, while in only 6% of cells it is located at the opposite pole. After 3 days in vitro, during the segregation of microtubule-associated proteins to either dendrites or axons. TGN38 immunoreactivity clusters continue to be located close to a major dendrite, and in some neurons these clusters begin to enter a major Map2-immunoreactive process. At 10 days in vitro TGN38 immunoreactivity extends into a major dendrite for 5-30 microns in many neurons. Thus, the distribution of TGN38 immunoreactivity becomes polarized, being localized within a single, usually the major, neocortical dendrite. Our results also show that the morphological appearance of TGN38-immunoreactive structures is microtubule-dependent, since nocodazole treatment of polarized neurons induces scattering of TGN38-immunoreactive vesicles throughout the cell body's cytoplasm. Treatment with brefeldin A induces scattering of small TGN38-immunoreactive vesicles throughout the neuronal cytoplasm and processes, a different response to that observed in non-neuronal cells.

Animals↗
PubMed1994

beta-Lactamase topology probe analysis of the OutO NMePhe peptidase, and six other Out protein components of the Erwinia carotovora general secretion pathway apparatus.

The out gene cluster of Erwinia spp. encodes the proteins of the general secretory pathway (GSP) apparatus that is required for pectinase and cellulase secretion. We have used fusions between Erwinia carotovora subsp. carotovora (Ecc) out genes and the topology probe blaM to assess the ability of Out protein regions to export BlaM across the cytoplasmic membrane in Escherichia coli and Ecc. For the outO gene product (an NMePhe peptidase), seven transmembrane regions have been identified and one more is predicted. The region of OutO with the highest level of hydrophilicity is likely to exist as a large cytoplasmic loop, located between two hydrophobic domains, and is positioned towards the N-terminus of the protein. When BlaM was fused on the C-terminal side of the last hydrophobic stretch of OutO, the resulting hybrid protein transferred the BlaM moiety to the periplasm whilst retaining OutO activity. Removal of a portion of this hydrophobic stretch resulted in the loss of OutO activity, suggesting that there are tight constraints on the topological integrity of OutO for maintaining catalytic function. When outG, -H, -I, -J, -K and -N were fused to blaM, the resulting phenotype suggested that the majority of each protein was targeted to the periplasm. Our results indicate that these six Out proteins, when produced by E. coli or Ecc, each adopt, at least temporarily, a type II bitopic conformation in the cytoplasmic membrane. For OutG, -H, -I and -J this probably represents the membrane topology prior to processing by OutO in Ecc. When produced in vivo from a T7 gene 10 promoter construct, the outG product was processed in Ecc whereas the outO mutant RJP249 failed to process pre-OutG. BlaM fusions positioned on the C-terminal side of the hydrophobic stretches of pre-OutG, -H, -I, and -J were processed by wild-type Ecc but not RJP249 or E. coli DH1. Thus the periplasmic domains of these proteins play no role in the peptidase cleavage reaction. An OutG-BlaM fusion construct was used to demonstrate NMePhe peptidase activity in other bacterial strains including E. carotovora subsp. carotovora (ATCC39048), E. carotovora subsp. atroseptica (SCRI1043) and Erwinia chrysanthemi (3937).

Amino Acid Sequence↗
PubMed1993

Third-body irradiation as an effective palliative treatment for painful multiple bone metastases resistant to chemo- or hormonal treatment.

Fifty-three patients had 54 third-body areas irradiated for breast and prostate bone metastases using the third-body irradiation technique during a period of 6 years. These patients were previously treated with chemotherapy, hormonal therapy and limited field irradiation. Seventy percent responded completely and 24% partially. This modality is safe and effective for pain relief.

Bone Neoplasms↗
PubMed1993

Molecular cloning and characterization of 13 out genes from Erwinia carotovora subspecies carotovora: genes encoding members of a general secretion pathway (GSP) widespread in gram-negative bacteria.

The chemical mutagen ethylmethanesulphonate (EMS) has been used to generate mutants of Erwinia carotovora subspecies carotovora which are defective in the secretion of pectinases (Pel) and cellulases (Cel) but unaltered for protease (Prt) secretion. Such mutants, called Out-, still synthesize Pel and Cel but these enzymes accumulate within the periplasm. Cosmid clones carrying wild-type E. carotovora ssp. carotovora DNA, identified by their ability to restore the Out+ phenotype when transferred to some Out- mutants, were classified into six complementation groups using cosmids and cosmid derivatives. Analysis of the nucleotide sequence of a 12.7 kb DNA fragment, encompassing complementing cosmid inserts, revealed a coding capacity for 13 potential open reading frames (ORFs), and these were designated outC-outO. Some of the out gene products were visualized using a T7 gene 10 expression system. The predicted Out proteins are highly similar to components of extracellular enzyme secretion systems from a diverse range of eubacteria including Erwinia chrysanthemi, Klebsiella oxytoca, Aeromonas hydrophila, Pseudomonas aeruginosa and Xanthomonas campestris. Lower levels of similarity exist between Ecc Out proteins and components of macromolecular trafficking systems from Bacillus subtilis, Haemophilus influenzae, Agrobacterium tumefaciens, Yersinia pestis and a protein involved in the morphogenesis of filamentous bacteriophages such as M13.

Amino Acid Sequence↗
PubMed1991

A developing complex odontome associated with delayed premolar formation.

Delayed development of a bicuspid in the right premolar region of the mandible was observed radiographically in a 16-year-old male patient following surgical removal of a developing odontome. Whilst odontomes are commonly associated with a failure of eruption of permanent teeth, this case was unusual in that there was both failure and marked delay of adjacent permanent tooth germ development, suggesting that the odontome was associated with a regional disturbance of odontogenic tissues in the neonatal period.

Adolescent↗
PubMed1989

[Brief intracavitary radiation (137 cesium) of the prostatic site in localized cancer of the prostate: preliminary results after 9 years].

Incidental detection of an adenocarcinoma's microscopic focus inside a piece of adenoma or TURP-chips is not rare. Generally, these hidden or "latent" carcinomas without any clinical event, are staged T0 (UICC) or stage A (Whitmore). In reviews, we can find justification of two contrasting attitudes: radical prostatectomy or therapeutic abstention. For the last nine years, we have proposed a third method: endocavitary curietherapy by 137 Cs of prostatic lodge, whose first results, in terms of morbidity and mortality, are discussed.

Adenocarcinoma↗
PubMed1988

Antianginal effects of intravenous nitroglycerin over 24 hours.

To determine the constancy of hemodynamic and antianginal effects of the constant infusion of intravenous nitroglycerin (NTG) and their relationship to infusion rate and plasma NTG concentration, we administered maximal tolerated doses of intravenous NTG (range 10 to 120 micrograms/min, mean = 52 +/- 33 micrograms/min) and placebo to 10 patients with chronic stable angina for 25 hr each in a randomized, double-blind fashion. Sublingual NTG (0.4 mg) was given at 24.5 hr of infusion as a positive control. Bicycle exercise time (NIH protocol), blood pressure, heart rate, exercise ST response, and venous plasma NTG were determined before and at 1, 4, 8, 24, and 24.5 hr. Plasma NTG was linearly related to infusion rate, reached a steady state within 15 min and was unchanged over 24 hr (mean = 5.5 +/- 1.2 ng/ml). Mean plasma NTG clearance was 9.3 liters/min. However, during dose titration, patients demonstrated different relationships between plasma NTG and hemodynamic effects, with widely varying slopes and intercepts. Intravenous NTG produced a sustained reduction in blood pressure and a rise in heart rate at rest, and a reduction in blood pressure during submaximal exercise at as late as 24 hr, associated with reduced submaximal ST segment abnormality. In contrast, exercise tolerance to onset of angina showed a marked initial increase on intravenous NTG but fell progressively and did not differ from that with placebo at 24 hr. Increased exercise tolerance was associated with an increase in maximal heart rate and double product (heart rate X blood pressure), suggesting that direct coronary vasodilation and/or reduced left ventricular volume were the principal determinants of increased exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed1987

[Immunoscintigraphy using radio-labeled monoclonal antibodies. Development of a method of cancer diagnosis and hopes for a new form of therapy].

Personal results are presented to illustrate the development of immunoscintigraphy for the detection of cancer over the last 12 years, from the early experimental results in nude mice grafted with human colon carcinoma to the most modern form of immunoscintigraphy applied to patients, using I123 labeled Fab fragments from monoclonal anti-CEA antibodies detected by single photon emission computerized tomography (SPECT). The first generation of immunoscintigraphy used I131 labeled, immunoadsorbent purified, polyclonal anti-CEA antibodies and planar scintigraphy, as the detection system. The second generation used I131 labeled monoclonal anti-CEA antibodies and SPECT, while the third generation employed I123 labeled fragments of monoclonal antibodies and SPECT. The improvement in the precision of tumor images with the most recent forms of immunoscintigraphy is obvious. However, we think the usefulness of immunoscintigraphy for routine cancer management has not yet been entirely demonstrated. Further prospective trials are still necessary to determine the precise clinical role of immunoscintigraphy. A case report is presented on a patient with two liver metastases from a sigmoid carcinoma, who received through the hepatic artery a therapeutic dose (100 mCi) of I131 coupled to 40 mg of a mixture of two high affinity anti-CEA monoclonal antibodies. Excellent localisation in the metastases of the I131 labeled antibodies was demonstrated by SPECT and the treatment was well tolerated. The irradiation dose to the tumor, however, was too low at 4300 rads (with 1075 rads to the normal liver and 88 rads to the bone marrow), and no evidence of tumor regression was obtained. Different approaches for increasing the irradiation dose delivered to the tumor by the antibodies are considered.

Animals↗
PubMed1987

Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects.

Chronic rapid ventricular pacing in the dog reportedly produces a useful preparation of low-output heart failure. However, little information is available regarding cardiac changes in this preparation. Accordingly, we evaluated the effects of both short-term (3 weeks) and prolonged (2 months) rapid ventricular pacing on cardiac hemodynamics, mass, and chamber size. The effects of short-term pacing on left ventricular wall thickening, blood flow, and metabolism were also examined. Compared with 16 control dogs, dogs paced for either 3 weeks (n = 8) or 2 months (n = 13) exhibited reduced cardiac outputs (control 130 +/- 20 ml/min/kg, 3 week pacing 112 +/- 19 ml/min/kg, 2 month pacing 116 +/- 14 ml/min/kg) and elevated pulmonary wedge pressures (control 10 +/- 3 mm Hg, 3 week pacing 26 +/- 5 mm Hg, 2 month pacing 26 +/- 8 mm Hg) and right atrial pressures (control 4 +/- 1 mm Hg, 3 week pacing 13 +/- 3 mm Hg, 2 month pacing 9 +/- 3 mm Hg) (all p less than .01 vs control). At the postmortem examination, both groups of paced dogs also exhibited increased left ventricular volumes (control 13 +/- 6 ml, 3 week pacing 27 +/- 6 ml, 2 month pacing 26 +/- 8 ml), right ventricular volumes (control 13 +/- 5 ml, 3 week pacing 27 +/- 9, 2 month pacing 24 +/- 7 ml), and right ventricular mass (control 27 +/- 5 g, 3 week pacing 32 +/- 6 g, 2 month pacing 34 +/- 6 g) (all p less than .03 vs control) but had normal left ventricular mass. Three weeks of pacing also decreased percent left ventricular shortening (34 +/- 6% to 17 +/- 7%) associated with a disproportionate deterioration of posterior wall thickening (58 +/- 16% to 17 +/- 18%) (both p less than .01), as assessed by echocardiography. This left ventricular dysfunction was associated with no change in myocardial lactate extraction (prepacing 40 +/- 10%, 3 week pacing 36 +/- 10%), myocardial arteriovenous O2 difference, or myocardial histology, suggesting that it was not due to myocardial ischemia. These data indicate that rapid ventricular pacing in the dog produces a useful experimental preparation of low-output heart failure characterized by biventricular pump dysfunction, biventricular cardiac dilation, and nonischemic impairment of left ventricular contractility.

Animals↗
PubMed1987

Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study.

We prospectively studied 16 patients with isolated aortic stenosis and eight with isolated aortic regurgitation undergoing aortic valve replacement, using two-dimensional echocardiography preoperatively, intraoperatively, and 41 +/- 7 days postoperatively to calculate the intraoperative change in afterload, quantify the postoperative changes in left ventricular chamber size, architecture, load and function, determine whether the postoperative left ventricular remodeling correlated with the intraoperative change in afterload in aortic stenosis and aortic regurgitation, and assess whether preoperative afterload excess precluded postoperative improvement in left ventricular function. Preoperative left ventricular mass, end-systolic meridional and circumferential wall stresses, ejection fraction, and stress-shortening relations in patients with aortic stenosis and aortic regurgitation were similar. However, our patients with aortic regurgitation had severe systolic dysfunction, with ejection fraction less than 55% in all but one patient, compared with only 10 of 16 patients with aortic stenosis. Left ventricular end-diastolic volume, mass/volume ratio, and chamber shape were significantly different in patients with aortic stenosis and aortic regurgitation (174 +/- 64 vs 294 +/- 140 ml, p less than .01; 1.81 +/- 0.63 vs 1.14 +/- 0.18, p less than .01; and 0.59 +/- 0.09 vs 0.69 +/- 0.09, p less than .05, respectively). Intraoperative end-systolic meridional and circumferential stresses fell significantly in patients with aortic stenosis but remained unchanged in those with aortic regurgitation. The changes in left ventricular volume and ejection fraction during early postoperative remodeling (6 weeks) correlated with the intraoperative change in afterload in patients with aortic stenosis. In contrast, there was no intraoperative change in afterload in patients with aortic regurgitation and no significant changes in left ventricular volume, architecture, or function at 6 weeks or at 6 months. The differences in left ventricular remodeling and changes in function between patients with aortic stenosis and aortic regurgitation in the early postoperative period most probably relates to the major difference in intraoperative reduction in afterload, although a contributory role may have been played by the preoperative left ventricular dysfunction in those with aortic regurgitation that was underestimated by measurement of ejection fraction.

Adult↗
PubMed1985

Effects of reduced left ventricular mass on chamber architecture, load, and function: a study of anorexia nervosa.

We investigated the effects of reduction in left ventricular mass on cavity geometry, afterload, pump function, and exercise performance in 17 patients with anorexia nervosa and in 10 age-and sex-matched normal subjects. Left ventricular mass index determined by two-dimensional echo-cardiography was significantly lower than that in normal subjects (53 +/- 15 vs 79 +/- 18 g/m2; p less than .005). Left ventricular end-diastolic and end-systolic volume indexes were also reduced in patients with anorexia nervosa compared with normal subjects (49 +/- 11 vs 65 +/- 17 ml/m2, p less than .005; 14 +/- 5 vs 19 +/- 4 ml/m2, p less than .025). In spite of the reductions in left ventricular mass and volume indexes, left ventricular chamber architecture described as h/R ratio, mass to volume ratio, and short/long left ventricular axis ratio were normal. Left ventricular afterload assessed as end-systolic meridional and circumferential wall stress was normal (59 +/- 18 vs 79 +/- 19 dyne/cm2 X 10(3) and 170 +/- 26 vs 167 +/- 23 dyne/cm2 X 10(3)). Ejection fraction, percent fractional shortening, and the relationship between end-systolic wall stress and ejection fraction were all within normal limits. In seven patients restudied after a 15% to 20% weight gain, left ventricular mass and volume indexes increased significantly but end-systolic wall stress and ejection fraction did not change. Ten patients with anorexia nervosa and resting heart rates and systolic blood pressures significantly lower than control values underwent treadmill testing. Exercise duration, peak heart rate, peak systolic blood pressure, and peak oxygen consumption in these patients were all significantly lower than normal. The hypotensive effect of fasting resulted in an initial decrease in afterload, which was the stimulus for reduction in left ventricular mass. The left ventricular remodeling associated with the mass reduction occurred in such a way that (1) orthogonal, meridional, and circumferential wall stresses were normalized, (2) normal chamber shape and architecture were maintained, and (3) chamber function and stress-shortening relationships were preserved. Thus down-regulation of left ventricular mass per se, like up-regulation of left ventricular mass, is not associated with abnormal left ventricular function.

Adolescent↗
PubMed1981

[Concentrated radiotherapy of brain metastases].

Presentation of 60 patients with cerebral metastases irradiated with a telecobaltotherapy machine (concentrated high dose treatment) from 1976 to 1979; 47 patients fully completed the treatment: 11 patients had only one part of the concentrated treatment and 36 patients had both parts of the concentrated treatment. Of the 11 patients who received only one part of the concentrated high dose treatment (3 x 650 rads mid-line dose to the whole brain during 3 consecutive days and then, after a rest period of 3 weeks, 12 x 170 rads mid-line dose given in two weeks using classical fractionation, total dose 3990 rads), 9 (81.8%) responded favourably with average survival of 5 months. Of the 36 patients who received both parts of the concentrated high dose treatment, i.e. 3 x 650 rads mid-line dose in 3 consecutive days and then the same treatment repeated 3 weeks later. giving a total dose of 3900 rads, 31 (86.1%) responded favourably with an average survival of 5 months. This type of regimen, using the two-part concentrated high dose treatment ("split course therapy"), not only spectacularly alleviated neurological signs and symptoms but had the added advantage of appreciably reducing the patients' stay in hospital.

Aged↗