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Biomedical subjects

P Powell

Publications and source records attributed to P Powell.

17 recordsLinked to original sources

Surveillance of adverse reactions in patients self-infusing intravenous immunoglobulin at home.

This is the first prospective study of adverse reactions occurring in primary-antibody-deficient patients self-infusing intravenous immunoglobulin at home. One hundred nineteen patients, already self-infusing at home, were entered into the study. They had been fully instructed about all aspects of adverse reactions, including their prevention and treatment. In the event of any adverse reaction, a form was completed detailing the product, the dose, the symptoms that occurred and the time they lasted, the rate of infusion, and other relative information such as predisposing factors and any medication taken. The severity of reactions were classified as mild, moderate, or severe. The total number of reactions documented was 19 in 2031 infusions, and all resolved without medical aid. No serious reactions occurred. Excluding those reactions in which predisposing factors were identified, the overall reaction rate was 0.7%. In conclusion the study showed the reaction rate in patients self-infusing intravenous immunoglobulin at home was low following formal training of selected patients at recognized training centers.

Adolescent

Hurricane Hugo blows down the broccoli: preschoolers' post-disaster play and adjustment.

This article reports highlights from over 200 parents' observations of their preschoolers' play and verbalizations in the year following Hurricane Hugo. Commonly reported activities included reenactment and discussion of the event in multiple mediums, personification of "Hugo", and expression of fears related to storms. Precocious concern for others, insight, and vocabulary were also noted. In these intact, relatively high functioning families, parents seemed able to facilitate their youngsters' adjustment without outside intervention.

Adaptation, Psychological

Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase.

The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2-thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes.

Adenylyl Cyclase Inhibitors

A cytosolic protein activator of cardiac sarcolemmal phosphoinositide phospholipase C.

Ca2+ dependent polyphosphoinositide phospholipase C (PLC) activity in cardiac sarcolemma hydrolyzed both endogenous and exogenous phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) with an associated increase in inositol bisphosphate (IP2). Dialyzed cytosol and certain fractions of cytosol isolated by anion exchange or gel filtration chromatography activated sarcolemmal PLC activity by approx. 100%. The PLC activator eluted with an apparent molecular weight of 160 Kdal on a Sephacryl 300 column and was destroyed by heat or trypsin treatment. Exogenous 3H-PIP2 was not hydrolyzed by cytosolic fractions containing sarcolemmal PLC activator. These studies demonstrate that the polyphosphoinositide PLC in cardiac sarcolemma is regulated by a cytosolic protein.

Animals

Regulation of polyphosphoinositide synthesis in cardiac membranes.

The relative distribution of phosphatidylinositol (PI) and phosphatidylinositol-4-phosphate (PIP) kinase activities in enriched cardiac sarcolemma (SL), sarcoplasmic reticulum (SR), and mitochondrial fractions was investigated. PI and PIP kinase activities were assayed by measuring 32P incorporation into PIP and phosphatidylinositol 4,5-bisphosphate (PIP2) from endogenous and exogenous PI in the presence of [gamma-32P]ATP. PI and PIP kinase activities were present in SL, SR, and mitochondrial fractions prepared from atria and ventricles although the highest activities were found in SL. A similar membrane distribution was found for PI kinase activity measured in the presence of detergent and exogenous PI. PI and PIP kinase activities were detectable in the cytosol providing exogenous PI and PIP and Triton X-100 were present. Further studies focused on characterizing the properties and regulation of PI and PIP kinase activities in ventricular SL. Alamethacin, a membrane permeabilizing antibiotic, increased 32P incorporation into PIP and PIP2 4-fold. PI and PIP kinase activities were Mg2+ dependent and plateaued within 15-20 min at 25 degrees C. Exogenous PIP and PIP2 (0.1 mM) had no effect on PIP and PIP2 labeling in SL in the absence of Triton X-100 but inhibited PI kinase activity in the presence of exogenous PI and Triton X-100. Apparent Km's of ATP for PI and PIP kinase were 133 and 57 microM, respectively. Neomycin increased PIP kinase activity 2- to 3-fold with minor effects on PI kinase activity. Calmidazolium and trifluoperazine activated PI kinase activity 5- to 20-fold and completely inhibited PIP kinase activity. Quercetin inhibited PIP kinase 66% without affecting PI kinase activity. NaF and guanosine 5'-O-(3-thiotriphosphate) had no effect on PI and PIP kinase activities, indicating that these enzymes were not modulated by G proteins. The probability that PIP and PIP2 synthesis in cardiac sarcolemma is regulated by product inhibition and phospholipase C was discussed.

Adenosine Triphosphate

Immunologically measured serum markers and their role in the management of prostate cancer.

Serum prostatic acid phosphatase and prostate-specific antigen have been measured in a group of 106 cases of newly diagnosed prostate cancer. The serum levels of the tumour markers have been correlated with the clinical and ultrasound staging of the prostate cancer at diagnosis. All patients were managed by a deferred treatment policy. Patients without detectable metastases at presentation have been assessed after a period of 2 years to determine if the level of serum tumour markers at diagnosis could predict subsequent disease progression. The study has demonstrated that a combination of immunologically measured acid phosphatase and prostate-specific antigen is the best method of assessing the prognosis of an individual prostate cancer at the time of presentation.

Acid Phosphatase

Medium-chain acyl coenzyme A dehydrogenase from pig kidney has intrinsic enoyl coenzyme A hydratase activity.

The flavoprotein medium-chain acyl coenzyme A (acyl-CoA) dehydrogenase from pig kidney exhibits an intrinsic hydratase activity toward crotonyl-CoA yielding L-3-hydroxybutyryl-CoA. The maximal turnover number of about 0.5 min-1 is 500-1000-fold slower than the dehydrogenation of butyryl-CoA using electron-transferring flavoprotein as terminal acceptor. trans-2-Octenoyl- and trans-2-hexadecenoyl-CoA are not hydrated significantly. Hydration is not due to contamination with the short-chain enoyl-CoA hydratase crotonase. Several lines of evidence suggest that hydration and dehydrogenation reactions probably utilize the same active site. These two activities are coordinately inhibited by 2-octynoyl-CoA and (methylenecyclopropyl)acetyl-CoA [whose targets are the protein and flavin adenine dinucleotide (FAD) moieties of the dehydrogenase, respectively]. The hydration of crotonyl-CoA is severely inhibited by octanoyl-CoA, a good substrate of the dehydrogenase. The apoenzyme is inactive as a hydratase but recovers activity on the addition of FAD. Compared with the hydratase activity of the native enzyme, the 8-fluoro-FAD enzyme exhibits a roughly 2-fold increased activity, whereas the 5-deaza-FAD dehydrogenase is only 20% as active. A mechanism for this unanticipated secondary activity of the acyl-CoA dehydrogenase is suggested.

Acyl-CoA Dehydrogenases

Polyphosphoinositides and the shape of mammalian erythrocytes.

The relationship between polyphosphoinositide and phosphatidic acid (PA) metabolism and Mg-ATP dependent shape and viscosity changes in erythrocyte ghosts from four mammalian species was examined. Ghosts prepared from rabbit, dog, human and guinea pig erythrocytes were transformed from echinocytes to discocytes within 15 min in the presence of 1 mM Mg-ATP at 25 C. In all species these Mg-ATP shape transformations were associated with a 30-45% decrease in the specific viscosity of the ghost suspensions. Mg-ATP induced a second transformation of discocytic ghosts to cup shape forms without a further decrease in viscosity. A considerable species variation in the rates of Mg-ATP dependent viscosity and shape changes and incorporation of 32P into phosphatidylinositol-4' phosphate (PIP), phosphatidylinositol-4'5'bisphosphate (PIP2) and especially PA from Mg-[gamma 32P]-ATP in ghosts was found. However, the rates of Mg-ATP dependent synthesis of PIP and PIP2 and shape and viscosity changes in each species were of the same magnitude. Ca2+ or neomycin strongly inhibited PIP labeling and Mg-ATP shape and viscosity changes in ghosts of the different species. Ca2+ or neomycin usually increased or had little effect on 32P incorporation into PA and PIP2. The possibility that Mg-ATP-induced changes in erythrocyte membrane shape and deformability are dependent on increases in membrane PIP and PIP2 is discussed.

Adenosine Triphosphate

Effects of tap water lead, water hardness, alcohol, and cigarettes on blood lead concentrations.

A survey of middle-aged men in 24 British towns has found pronounced geographical variation in blood lead concentrations. Towns with the highest mean blood lead concentrations have soft water supplies and have the highest water lead concentrations. Individual blood lead can be considerably increased by raised household tap water lead concentrations. Mean blood lead is estimated to be 43% higher for men when the concentration of lead in first-draw domestic tap water is 100 micrograms/l compared with a zero concentration. Individual blood lead is also affected by alcohol consumption and cigarette smoking, such that on average these two life-style habits together contribute an estimated 17% to the blood concentration of lead in middle-aged men. Lead in water should be given greater priority in any national campaign to reduce lead exposure.

Adult

Muscle fiber type distribution and architecture of the cat diaphragm.

Three types of diaphragmatic muscle fibers were identified histochemically in the sternal, costal, and crural regions of the cat diaphragm. Differences in the proportion of each muscle fiber type were observed between the abdominal and thoracic surfaces of the diaphragm but not among the different regions. A higher percentage of slow-twitch oxidative fibers was noted on the abdominal surface, whereas more fast-twitch fibers (fast-twitch oxidative-glycolytic and fast-twitch glycolytic) were found on the thoracic surface. Differences in muscle architecture were observed between diaphragmatic regions, but not between abdominal and thoracic sides. Overall, muscle fibers were longer in the crural regions, with the longest fibers being found in the crossing-band area of the crura. In the costal regions, fibers were longest in the center and became shorter toward the ventral and dorsal extent of these regions. Fiber lengths were similar throughout the sternal region. In each diaphragmatic region, the length of fibers extended from the origin of the muscle to its insertion. We conclude that functional differences between diaphragmatic regions could be attributed to fiber length and/or orientation, but not to differences in fiber-type composition.

Animals

Activation of the alternative complement pathway by normal and transformed cells in homologous and heterologous sera.

A variety of both normal and viral transformed or infected cells have been tested for their ability to activate the alternative pathway of complement in either homologous or heterologous sera. Normal cell lines fail to produce alternative pathway activation in homologous sera but readily activate the alternative pathway in heterologous sera. In contrast, human cells, persistently infected with measles virus or chicken cells transformed with oncogenic avian viruses, produce a marked activation in homologous sera. It is suggested that in certain circumstances, the alternative pathway of complement can discriminate between normal and abnormal "self" cells of foreign cell surfaces.

Animals

British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality.

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality-namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0.25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1.7 mmol/l (170 mg/l), while any further increase in hardness beyond 1.7 mmol/l did not additionally lower cardiovascular mortality.Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.

Adult

Cryptic mycotic abdominal aortic aneurysms: diagnosis and management.

The incidence of cryptic mycotic abdominal aortic aneurysms has relatively increased since antibiotic therapy has become available. The causative organism is the salmonella group in about 50 per cent of cases. This diagnosis should be strongly entertained in patients with fever of unknown origin, vague abdominal pain, and progressive appearance of a pulsatile abdominal mass. Aortography may be helpful in establishing the diagnosis. Some postoperative graft infections may be due to unrecognized cryptic mycotic infection of the aorta and not from external contamination, as previously supposed. Construction of an axillofemoral bypass graft through clean tissue is advised for the successful treatment of the grossly infected infrarenal aortic aneurysm. Three surviving patients with cryptic mycotic abdominal aortic aneurysms are added to the sixteen surviving patients already reported in the literature.

Aged

Endarterectomy of the internal carotid artery.

Results of 219 operations in 171 patients for arteriosclerotic stenosis of the internal carotid artery were consistently good in patients with lateralizing, transient ischemic attacks. Although less consistent, relief of symptoms may be expected in a high proportion of patients with significant stenosis and more nonspecific symptoms. A small number of patients (10 percent) may have significant stenosis without a bruit. Asymptomatic stenosis, which has an unpredictable prognosis, may be operated upon with low mortality and morbidity. The use of local anesthesia and shunting when necessary proved to be the safest technique for the authors.

Adult