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Biomedical subjects

L Harker

Publications and source records attributed to L Harker.

At least 19 recordsLinked to original sources

Beta-cell function and visceral fat in lactating women with a history of gestational diabetes.

Lactation has been recommended as beneficial for the maternal metabolic abnormalities associated with glucose intolerance and diabetes risk, although associations between breastfeeding (BF), glucose tolerance, and adipose tissue distribution are unknown. Therefore, a population of women with recent gestational diabetes (GDM) was evaluated with comparison of results for lactating versus nonlactating women. A total of 26 women participated (14 BF and 12 nonbreastfeeding [nonBF]) with a singleton vaginal delivery after 36 weeks gestation. At 3 months postpartum, each woman completed a 75-g oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), and computed tomography (CT) scanning for adipose distribution and mass. Insulin sensitivity was not significantly different between BF and nonBF groups (4.97 +/- 0.78 v 3.44 +/- 1.0 x 10(-4) min(-1)/(microU/mL) nor was glucose effectiveness (1.92 +/- 0.22 v 1.56 +/- 0.19 x 10(-2) min(-1)). However, the disposition index (DI) (insulin sensitivity [S(I)] x acute insulin response to glucose [AIRg]) was higher in the BF group (129.9 +/- 26.0 v 53.4 +/- 18.0 x 10(-4) min(-1); P =.03). Visceral fat (103 +/- 14 v 97 +/- 15 cm(2)) and subcutaneous fat (362 +/- 36 v 460 +/- 68 cm(2)) were similar between the groups. We conclude that 3 months of BF in a population with previous GDM was associated with improved pancreatic beta-cell function, but not with any difference in measures of adiposity.

Adipose Tissue↗

Expressions of positive emotion in women's college yearbook pictures and their relationship to personality and life outcomes across adulthood.

To test hypotheses about positive emotion, the authors examined the relationship of positive emotional expression in women's college pictures to personality, observer ratings, and life outcomes. Consistent with the notion that positive emotions help build personal resources, positive emotional expression correlated with the self-reported personality traits of affiliation, competence, and low negative emotionality across adulthood and predicted changes in competence and negative emotionality. Observers rated women displaying more positive emotion more favorably on several personality dimensions and expected interactions with them to be more rewarding; thus, demonstrating the beneficial social consequences of positive emotions. Finally, positive emotional expression predicted favorable outcomes in marriage and personal well-being up to 30 years later. Controlling for physical attractiveness and social desirability had little impact on these findings.

Adult↗

Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer.

BACKGROUND: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy. METHODS: We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given. RESULTS: In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base-line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis. CONCLUSIONS: MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.

Adult↗

Transcortical and cervical magnetic stimulation with recording of the diaphragm.

Transcortical and cervical magnetic stimulation is a potential method of examining the central inspiratory pathway to phrenic motor neurons. The reliability and accuracy of this technique were studied. We performed magnetic stimulations of the cortex and cervical spinal cord with recording from both hemidiaphragms in 35 normal subjects using two different stimulation coils (90-mm circular coil and 70-mm figure-of-eight coil). Needle electrode recordings and ultrasound real-time documentation in 2 subjects excluded volume-conducted contaminations from adjacent chest wall and abdominal muscles. The effect of diaphragmatic facilitation (stimulation at the end of a deep breath) on latency, and amplitude were compared to the effect of hypothenar muscle facilitation. Normal ranges were established for: latency; central motor conduction time; amplitude; amplitude ratio between between peripheral and both cortical and cervical amplitude; and excitability threshold. The latencies were similar for both coils. The amplitudes were significantly higher, and excitability thresholds significantly lower for the 90-mm circular coil, indicating that this coil is preferable for transcortical diaphragmatic stimulations. The effect of facilitation was greater for hypothenar than diaphragmatic recordings. There was excellent right-left agreement for all measurements. Transcortical and cervical magnetic stimulation with recording from the diaphragm can be used routinely to diagnose and monitor patients with impaired central respiratory drive.

Action Potentials↗

Women's views of ultrasonography. A comparison of women's experiences of antenatal ultrasound screening with cerebral ultrasound of their newborn infant.

Ultrasound screening is now a routine procedure which forms part of antenatal care provision. Within this routine context ultrasound technology has been found to be generally acceptable and indeed is positively demanded by many women. This paper raises the question whether the routine presentation of ultrasound implicitly conveys the message that its use in antenatal care is both valuable and safe. It examines women's views of ultrasound technology beyond a routine context. In study designed to examine women's reactions to cerebral ultrasound on their normal term infants mothers were asked their views and knowledge of ultrasound and a comparison with their antenatal experience of ultrasound was elicited. A generalized concern about ultrasound techniques was found to underlie many of the women's comments. This raised questions concerning the current practice in the presentation of ultrasound to women attending for antenatal care.

Attitude to Health↗

Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: a randomized, placebo-controlled trial of human surfactant.

We compared the neurodevelopmental outcome of extremely premature, surfactant-deficient infants who received either prophylactic surfactant at birth, "rescue" surfactant after the clinical diagnosis of respiratory distress syndrome was established, or placebo. Infants studied were participants in a randomized, bicenter (San Diego, Calif., and Helsinki, Finland), controlled trial of human surfactant therapy. One hundred fifty infants (prophylaxis group, 63 infants; rescue group, 57; placebo group, 30) were prospectively enrolled at 38 weeks of gestational age. There were no neonatal intergroup differences in the incidence or severity of sonographic central nervous system abnormality or retinopathy. One hundred forty-five infants were alive at 1 year of adjusted age, at which time growth, neurosensory, and neurologic outcome were similar in all three treatment groups at both centers. Cerebral palsy occurred in 20% overall. Five infants (3.5%) were functionally blind. However, infants treated at birth had lower mean mental and motor scores on the Bayley Scales of Infant Development compared with those of infants rescued with surfactant after the onset of respiratory distress syndrome (Mental Development Index: 78 vs 96, p = 0.02; Psychomotor Development Index: 73 vs 87, p = 0.04). Chronic lung disease occurred more frequently in the prophylactically treated group and contributed to the subjects' neurologic and developmental morbidity. Because prophylactic surfactant treatment offered no neurodevelopmental advantage and may contribute to poorer outcome, we currently recommend early surfactant replacement only for those infants who have postnatal evidence of respiratory distress syndrome.

Brain↗

"The last egg in the basket?" elderly primiparity--a review of findings.

The recent trend of later childbearing among primiparous women is examined with attention to its possible motivations and how they might relate to maternal and infant outcomes. The influence of psychological factors is examined in the context of the inconsistencies in the obstetric literature' regarding the risk factors associated with advancing maternal age. An interplay of psychological and biologic factors in determining the outcome of pregnancy and adaptation to motherhood in elderly primiparous women is proposed in terms of the compensatory as opposed to cumulative effect of psychological factors. The adoption of a broad perspective in the study of the experience of later motherhood is recommended as the direction for future research.

Adult↗

Radiologic findings of retroperitoneal perforation after sphincterotomy.

The radiographs of all patients with perforation into the retroperitoneum following endoscopic sphincterotomy, performed between 1981 to 1984 at University Hospital, London, Ontario were reviewed retrospectively. The incidence of perforation was very low. There were only three patients with perforation (1.1%), although 264 sphincterotomies had been performed. The initial and most important radiological findings are air and contrast medium in the retroperitoneum outlining the right kidney; a mottled air and soft tissue density in the right anterior pararenal space due to leak of duodenal contents, bile and air; or both of these findings together. With ultrasonography, a right paranephric fluid collection or an inflammatory mass adjacent to the right kidney or both may be better visualized. Computed tomography, the definitive study, delineates the true extent of the fluid or mass in the anterior pararenal space. Early detection by the radiologist is mandatory to minimize morbidity. To make this diagnosis early requires a high index of suspicion when reviewing the abdominal radiographs of those patients with pain during, or a few hours after, sphincterotomy.

Aged↗

Selective inhibition of thromboxane synthesis during experimental endotoxemia in the goat: effects on pulmonary haemodynamics and lung lymph flow.

1 The effects of a selective thromboxane synthetase inhibitor, dazoxiben (UK 37248), on haemodynamics, eicosanoid levels, and lung vascular permeability were assessed in three unanesthetized goats with chronic lung lymph fistulae following infusions of E. coli endotoxin (1 microgram/kg). Each animal received an infusion of endotoxin in both a control and treatment trial. In the control trial endotoxin alone was infused. In the treatment trial endotoxin administration was preceded by a bolus intravenous infusion of dazoxiben 25 mg/kg followed by a maintenance infusion of 10 mg/kg/h. 2 In animals receiving endotoxin alone the peak elevation in pulmonary artery and wedge pressures, the initial increase in lymph flow, and the fall in cardiac output correlated with the peak elevation in plasma thromboxane B2 (TXB2) concentration at 30 min after endotoxin. Although TXB2 levels had returned to baseline by 3 h, lung lymph flow remained elevated for at least 6 h after endotoxin. The lymph/plasma protein ratio (L/P) did not fall. 3 In dazoxiben-treated animals the rise in plasma concentrations of TXB2 after endotoxin was prevented and, in concert, the increase in pulmonary artery and wedge pressures, the fall in cardiac output, and the initial increase in lymph flow were greatly attenuated. The increase in lymph flow at 2-6 h after endotoxin, however, was not prevented in dazoxiben-treated animals, and again L/P did not change. 4 Plasma 6-keto-prostaglandin F1 alpha concentrations were not significantly altered by dazoxiben treatment except for an earlier peak. 5 We conclude that selective total inhibition of thromboxane synthesis can be achieved by dazoxiben. The inhibition ameliorates many of the adverse haemodynamic consequences of experimental endotoxaemia and reduces, but does not prevent pulmonary oedema formation. This seems to be due to an increase in lung microvascular permeability which is not mediated by TXA2.

Animals↗

Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.

The effect of dazoxiben, a selective thromboxane (Tx) synthetase inhibitor, on systemic and pulmonary hemodynamics, eicosanoids, and lung permeability was assessed in awake goats with lung lymph fistulae following infusion of Escherichia coli endotoxin (1 microgram/kg). Animals received endotoxin either with no treatment or pretreatment with a bolus (25 mg/kg) followed by a maintenance infusion (10 mg/kg per h) of dazoxiben. In untreated animals, the peak rise of 26.8 cm H2O in pulmonary artery (Ppa) and of 13.5 cm H2O in wedge (Pw) pressures occurred at the same time as the peak elevations in plasma thromboxane B2 (T X B2). Maximum reduction in cardiac output (Qt) also occurred at the same time. Lung lymph flow (QL) increased during this period and remained elevated for at least 6 h after endotoxin. T X B2 levels had returned from a peak of 13.1 to 0.7 ng/ml by 2 h. In dazoxiben-treated animals, plasma concentrations of T X B2 were never significantly elevated. Increases in Ppa and Pw were markedly reduced and decreased Qt was transient. QL in treated animals began to increase by 30 min after endotoxin and reached a peak by 2 h. Increased QL in treated animals was not as great as in the untreated animals. Moreover, lymph-plasma protein ratios increased significantly in treated animals. Plasma prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha concentrations were elevated in both groups after endotoxin with values significantly greater in treated animals. We conclude that selective inhibition of Tx ameliorates many adverse hemodynamic consequences of endotoxemia but does not prevent lung permeability changes.

Animals↗

Ulcerative colitis and sensorineural hearing loss: is there a relationship?

A number of systemic complications are recognized in patients with ulcerative colitis. We describe a patient with this disease who developed severe bilateral sensorineural hearing loss and vestibular dysfunction. Her hearing deficit improved dramatically with corticosteroids and cyclophosphamide therapy. The association between these two conditions has not previously been reported.

Adult↗

Platelets, endothelium, and smooth muscle cells in atherosclerosis.

A factor derived from platelets stimulates the proliferation of smooth muscle cells in culture, and is likely important in stimulating smooth muscle proliferative lesions of atherogenesis in vivo. The platelet factor is produced during platelet aggregation when serum is made from whole blood. In vitro, smooth muscle cells are potent aggregating agents for platelets, while endothelial cells can inhibit this aggregating effect. Better understanding of the interactions of platelets, smooth muscle cells, and endothelium would facilitate developing effective means of intervening in or preventing the smooth muscle proliferative lesions of atherosclerosis.

Animals↗

Response to injury and atherogenesis.

We postulate that the lesions of atherosclerosis arise as a result of some form of "injury" to arterial endothelium. This injury somehow results in alteration in endothelial cell-cell attachment or endothelial cell-connective tissue attachment, so that forces such as those derived from the shear in the flow of blood result in focal desquamation of endothelium. This is followed by adherence, aggregation, and release of platelets at the sites of focal injury. During the process of release, a mitogenic factor is secreted from the platelets which, together with plasma constituents, gains entry into the artery wall, resulting in focal intimal proliferation of smooth muscle cells. This intimal proliferation is accompanied by the synthesis of new connective tissue matrix proteins and often by the deposition of intracellular and extracellular lipids. Studies in cell culture of arterial smooth muscle have demonstrated that the principle mitogen present in blood serum is a platelet-derived factor that is present in all whole blood sera and missing in serum derived from platelet-free plasma. In the absence of the platelet factor, smooth muscle cells are quiescent in culture. This platelet mitogen is also active in vivo, since experimentally produced lesion of atherosclerosis induced mechanically by diet or by homocystine can be prevented if platelets are missing, as in thrombocytopenia, or if platelet function is impaired as a result of the use of platelet inhibitors such as dipyridamole. These studies point to the key role of the platelet in the stimulation of intimal smooth muscle proliferation that leads to the development of lesions of atherosclerosis.

Arteries↗