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Biomedical subjects

K Campbell

Publications and source records attributed to K Campbell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations.

A group of 79 renal transplant patients undergoing acute rejection episodes were treated with Thymoglobulin (rabbit anti-thymocyte globulin), 1.5 mg/kg/day for 6-14 days as part of a double-blinded trial comparing the efficacy of Thymoglobulin and Atgam (horse anti-thymocyte globulin). Serial serum samples from the patients were tested to determine the level of Thymoglobulin (i.e. rabbit IgG levels = total Thymoglobulin) and anti-Thymoglobulin using ELISAs. Antibodies binding to human lymphocytes (active Thymoglobulin), were determined by flow cytometry; no correlation was seen between treatment efficacy and either active or total Thymoglobulin concentrations; the overall treatment success rate was 86%. Pharmacokinetics of total and active Thymoglobulin were distinctly different; active Thymoglobulin disappeared much more rapidly: only 12% of patients had detectable active Thymoglobulin by day 90 compared to 81% of patients with detectable total Thymoglobulin; percent active Thymoglobulin decreased from a peak of 0.56-0.7% during treatment, to 0.07-0.35% by day 21, and less than 0.14% by day 30. Thymoglobulin and active Thymoglobulin concentrations were modeled by multiple regression. Using dose number and sensitization as independent variables, 47-76% of the variability seen in interpatient Thymoglobulin levels could be explained, while for active Thymoglobulin levels, the measured variables accounted for 13-48% of the observed interpatient variation. We conclude that: (1) for a group of patients receiving primary Thymoglobulin treatment (averaging nine full and one partial dose per patient), neither Thymoglobulin nor active Thymoglobulin levels are predictive of treatment outcome; (2) active Thymoglobulin disappears more rapidly from the circulation than total Thymoglobulin; and (3) patients that develop anti-rabbit IgG antibodies clear Thymoglobulin and active Thymoglobulin more rapidly than unsensitized patients.

Animals↗
PubMed2001

Provision of platelet support for fetuses and neonates affected by severe fetomaternal alloimmune thrombocytopenia.

Severe fetomaternal alloimmune thrombocytopenia requires urgent treatment with compatible platelet concentrates. As prompt treatment is sometimes delayed owing to the unavailability of compatible platelets, we established an accredited platelet donor panel to provide effective and timely transfusion support for fetal and neonatal therapy. After a mass screening programme of over 60,000 blood donations, 45 HPA-1a-negative donors with no antibodies to HPA, HLA, red cell antigens and granulocytes/lymphocytes, and with low titre anti-A and/or -B were accredited. All accredited donors were fully genotyped for HPA-1, -2, -3 and -5 by PCR-SSP. Ninety-one per cent of the accredited donors were also negative for HPA-5b.

Antigens, Human Platelet↗
PubMed2001

Interventions for preventing obesity in childhood. A systematic review.

BACKGROUND: The prevalence of obesity and overweight is increasing worldwide. Obesity in children impacts on their health in both short- and long-term. Obesity prevention strategies are poorly understood. OBJECTIVE: To assess the effectiveness of interventions designed to prevent obesity in childhood. SEARCH STRATEGY: Electronic databases were searched from January 1985 to October 1999. SELECTION CRITERIA: Data from randomized control trials and non-randomized trials with concurrent control group were included. A priori, studies with follow up of 1 year minimum were selected however, this was subsequently amended to include studies with a minimum follow up of three months. DATA COLLECTION & ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Seven studies were included, three long-term (> 1 years) and four short-term (> 3 months and < 1 years). The studies included were diverse in terms of study design and quality, target population, theoretical underpinning of intervention approach, and outcome measures. As such, it was not appropriate to combine study findings using statistical methods. CONCLUSIONS: Two of the long-term studies (one focused on dietary education and physical activity vs. control, and the other only on dietary education vs. control), resulted in a reduction in the prevalence on obesity, but the third, which focused on dietary education and physical activity, found no effect. Of the four short-term studies, three focused simply on physical activity/reduction of sedentary behavious vs. control. Two of these studies resulted in a reduction in the prevalence of obesity in intervention groups compared with control groups, and another study found a non-significant reduction. The fourth study focused on dietary education and physical activity, and did not find an effect on obesity, but did report a reduction in fat intake. Overall, the findings of the review suggest that currently there is limited quality data on the effectiveness of obesity prevention programmes and as such no generalizable conclusions can be drawn. The need for well-designed studies that examine a range of interventions remains a priority.

Child↗
PubMed2001

Effects of an external nasal dilator on the work of breathing during exercise.

PURPOSE: The effect of an external nasal dilator on the work of breathing (WOB) was measured during exercise in 14 untrained college students (age, 23 +/- 2.7 yr). METHODS: Two maximal, incremental ergometer tests were performed to exhaustion. Subjects wore a placebo or an active nasal dilator strip, in random order, during each test. An esophageal balloon was placed through each of the subject's mouth into the esophagus for measurement of inspiratory elastic work (INEW), inspiratory resistive work (INRW), and expiratory resistive work (EXRW). Subjects breathed through a Hans Rudolph(R) face mask that covered both the mouth and nose during both tests. Measured variables included oxygen uptake (VO2), ventilation (VE), tidal volume (VT), frequency of breathing (f), INEW, INRW, and EXRW (work expressed in joules). An alpha level was set at P < 0.05. RESULTS: No significant differences were found in INEW, INRW, and EXRW between conditions at 70% of VO2max (mean +/- SD; Placebo: INEW, 25.6 +/- 17.8 J.min-1; INRW, 22.4 +/- 15.8 J.min-1; EXRW, 16.7 +/- 12.3 J.min-1; Active: INEW, 24.7 +/- 12.9 J.min-1; INRW, 19.7 +/- 11.9 J.min-1; EXRW, 15.2 +/- 8.6 J.min-1; P > 0.05). No difference was found in INEW, INRW, and EXRW at maximal exercise between conditions (mean +/- SD; Placebo: INEW, 50.2 +/- 29.9 J.min-1; INRW, 67.3 +/- 42.3 J.min-1; EXRW, 102.3 +/- 78.4 J.min-1; Active: INEW, 45.7 +/- 19.6 J.min-1; INRW, 62.6 +/- 36.7 J.min-1; EXRW, 86.3 +/- 50.9 J.min-1; P > 0.05). There were no differences in VO2, VE, VT, or f between conditions. CONCLUSION: Wearing an external nasal dilator does not significantly reduce the work of breathing during exercise.

Adult↗
PubMed2001

Emergency redo mitral valve replacement in a 27-year-old pregnant female with a clotted prosthetic mitral valve, preoperative fetal demise and postoperative ventricular assist device: a case report.

A 27-year-old Laotian woman with a St Jude mechanical mitral valve became pregnant, requiring a change in her anticoagulant after the first trimester when her warfarin sodium (coumadin) was replaced with enoxaparin sodium (lovenox). Her prosthetic valve clotted and became dysfunctional. She was 16 weeks pregnant and was taken to the operating room for emergency surgery for replacement of the valve. The fetus had not been viable for 1-2 weeks, but still remained in utero. The clotted valve was replaced with another St Jude valve of a slightly smaller diameter (27 mm). The patient could not be weaned from bypass so a right ventricular assist device (RVAD) was inserted. The patient was weaned from the RVAD after 2 days of support. Two days following removal of the RVAD the fetus spontaneously aborted. The patient had a long, complicated hospital course and was discharged 3 months later. She subsequently died 4 months after discharge of a cerebral hemorrhage from excessive anticoagulation.

Adult↗
PubMed2001

A role for Gsh1 in the developing striatum and olfactory bulb of Gsh2 mutant mice.

We have examined the role of the two closely related homeobox genes Gsh1 and Gsh2, in the development of the striatum and the olfactory bulb. These two genes are expressed in a partially overlapping pattern by ventricular zone progenitors of the ventral telencephalon. Gsh2 is expressed in both of the ganglionic eminences while Gsh1 is largely confined to the medial ganglionic eminence. Previous studies have shown that Gsh2(-/-) embryos suffer from an early misspecification of precursors in the lateral ganglionic eminence (LGE) leading to disruptions in striatal and olfactory bulb development. This molecular misspecification is present only in early precursor cells while at later stages the molecular identity of these cells appears to be normalized. Concomitant with this normalization, Gsh1 expression is notably expanded in the Gsh2(-/-) LGE. While no obvious defects in striatal or olfactory bulb development were detected in Gsh1(-/-) embryos, Gsh1/2 double homozygous mutants displayed more severe disruptions than were observed in the Gsh2 mutant alone. Accordingly, the molecular identity of LGE precursors in the double mutant is considerably more perturbed than in Gsh2 single mutants. These findings, therefore, demonstrate an important role for Gsh1 in the development of the striatum and olfactory bulb of Gsh2 mutant mice. In addition, our data indicate a role for Gsh genes in controlling the size of the LGE precursor pools, since decreasing copies of Gsh2 and Gsh1 alleles results in a notable decrease in precursor cell number, particularly in the subventricular zone.

Animals↗
PubMed2000

Nud1p links astral microtubule organization and the control of exit from mitosis.

The budding yeast spindle pole body (SPB) not only organizes the astral and nuclear microtubules but is also associated with a number of cell-cycle regulators that control mitotic exit. Here, we describe that the core SPB component Nud1p is a key protein that functions in both processes. The astral microtubule organizing function of Nud1p is mediated by its interaction with the gamma-tubulin complex binding protein Spc72p. This function of Nud1p is distinct from its role in cell-cycle control: Nud1p binds the spindle checkpoint control proteins Bfa1p and Bub2p to the SPB, and is part of the mitotic exit network (MEN) in which it functions upstream of CDC15 but downstream of LTE1. In conditional lethal nud1-2 cells, the MEN component Tem1p, a GTPase, is mislocalized, whereas the kinase Cdc15p is still associated with the SPB. Thus, in nud1-2 cells the failure of Tem1p to interact with Cdc15p at the SPB probably prevents mitotic exit.

Animals↗
PubMed2000

High-performance liquid chromatographic determination of 17beta-estradiol and 17beta-estradiol-3-acetate solubilities and diffusion coefficents in silicone elastromeric intravaginal rings.

A rapid, sensitive reversed-phase high-performance liquid chromatographic method has been developed for the determination of in vitro release of 17beta-estradiol and its ester prodrug, 17beta-estradiol-3-acetate, from silicone intravaginal rings. Partial hydrolysis of the acetate under the aqueous conditions provided by the 1% benzalkonium chloride release medium necessitates its conversion to 17beta-estradiol prior to HPLC analysis. Both steroid peaks have been fully resolved from the benzalkonium chloride peaks by the reported chromatographic method, which employs a C18 bonded reversed-phase column, an acetonitrile-water (50:50, v/v) mobile phase and a UV detection wavelength of 281 nm. The peak area versus 17beta-estradiol concentration was found to be linear over the range of 0.0137-1347 microkg ml(-1). The HPLC method has also been used to determine the silicone solubilities and diffusion coefficients of the two related steroids. The almost 100-fold increase in 17beta-estradiol-3-acetate release from the silicone core-type intravaginal rings compared to 17beta-estradiol is shown to be due to a 60-fold increase in silicone solubility and a one and a half-fold increase in diffusitivity. The results demonstrate that an effective estrogen replacement therapy dose of 17beta-estradiol may be administered from a silicone intravaginal reservoir device containing the labile 17beta-estradiol-3-acetate prodrug.

Administration, Intravaginal↗
PubMed2000

Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery.

In this study it has been demonstrated that mixtures of two solid drugs, ibuprofen and methyl nicotinate, with different but complementary pharmacological activities and which exist as a single liquid phase over a wide composition range at skin temperature, can be formulated as o/w emulsions without the use of an additional hydrophobic carrier. These novel dual drug systems provided significantly enhanced in vitro penetration rates through a model lipophilic barrier membrane compared to conventional individual formulations of each active. Thus, for ibuprofen, drug penetration flux enhancements of three- and 10-fold were observed when compared to an aqueous ibuprofen suspension and a commercial alcohol-based ibuprofen formulation, respectively. Methyl nicotinate penetration rates were shown to be similar for aqueous gels and emulsified systems. Mechanisms explaining these observations are proposed. Novel dual drug formulations of ibuprofen and methyl nicotinate, formulated within the liquid range at skin temperature, were investigated by oscillatory rheology and texture profile analysis, demonstrating the effects of drug and viscosity enhancer concentrations, and disperse phase type upon the rheological, mechanical and drug penetration properties of these systems.

Administration, Topical↗
PubMed2000

A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's Disease Cooperative Study.

BACKGROUND: Laboratory and epidemiologic studies suggest that anti-inflammatory/immunosuppressive therapy may be useful in the treatment of AD. In preliminary studies, a regimen of low to moderate dose prednisone was found to suppress peripheral inflammatory markers without adverse effects in subjects with AD. METHODS: We conducted a randomized, placebo-controlled multicenter trial to determine whether prednisone treatment slowed the rate of cognitive decline in AD. The active treatment regimen consisted of an initial dose of 20 mg of prednisone daily for 4 weeks tapered to a maintenance dose of 10 mg daily for 1 year, followed by gradual withdrawal during an additional 16 weeks. The primary outcome measure was the 1-year change in the cognitive subscale of the AD Assessment Scale. RESULTS: A total of 138 subjects were randomized to the drug and placebo groups. There was no difference in cognitive decline between the prednisone and placebo treatment groups in the primary intent-to-treat analysis, or in a secondary analysis considering completers only. Subjects treated with prednisone showed behavioral decline compared with those in the placebo group. CONCLUSION: A low-dose regimen of prednisone is not useful in the treatment of AD.

Aged↗
PubMed2000

B-myb alters the response of myeloid precursor cells to G-CSF.

The human B-myb gene encodes a cell cycle-regulated DNA-binding phosphoprotein which functions as a transcription factor with an important role in cell cycle progression, survival, and differentiation. Recently, it has been demonstrated that ectopic murine B-myb expression blocked the ability of 32Dcl3 cells to proliferate in response to granulocyte colony-stimulating factor (G-CSF) and accelerated the induction of terminal differentiation. In contrast, we report that while 32Dcl3 cells overexpressing human B-myb do display some markers of myeloid differentiation earlier than parental cells, including the expression of myeloperoxidase mRNA and the appearance of band myelocytes in G-CSF-induced cultures, the induction of late markers of differentiation is inhibited. The expression of lactoferrin mRNA is absent and the appearance of terminally differentiated polymorphonuclear cells is severely impaired in B-myb-expressing 32Dcl3 cells. Furthermore, continuous exposure to G-CSF results in the outgrowth of a culture which expresses increased levels of B-myb RNA and is dependent on G-CSF for proliferation while retaining responsiveness to interleukin-3. These data suggest that the B-myb gene is involved in early transcriptional events during myeloid differentiation, but that its expression prevents terminal differentiation.

Animals↗
PubMed2000

Inhibition of eosinophilic inflammation in allergen-challenged, IL-1 receptor type 1-deficient mice is associated with reduced eosinophil rolling and adhesion on vascular endothelium.

To determine the relative in vivo importance of IL-1 release after allergen challenge to the subsequent endothelial adhesion and recruitment of eosinophils, the authors used ovalbumin sensitization and inhalation challenge to induce airway eosinophilia in IL-1 receptor type 1-deficient and control wild-type mice. Bronchoalveolar lavage (BAL) eosinophil recruitment in IL-1 receptor type 1-deficient mice challenged with ovalbumin (24.3% +/- 6.3% BAL eosinophils) was significantly reduced compared with wild-type mice (63.7% +/- 2.5% BAL eosinophils). To determine whether the inhibition of eosinophil adhesion to vascular endothelium contributed to the inhibition of eosinophil recruitment in IL-1 receptor type 1-deficient mice, the authors used intravital microscopy to visualize the rolling and firm adhesion of fluorescence-labeled mouse eosinophils in the microvasculature of the allergen-challenged mouse mesentery. Eosinophil rolling, eosinophil firm adhesion to endothelium, and transmigration across endothelium (peritoneal eosinophils) were significantly inhibited in allergen-challenged IL-1 receptor type 1-deficient mice compared with wild-type mice. Overall, these studies demonstrate that cytokines such as IL-1, released after allergen challenge, are important in the induction of endothelial cell adhesiveness, a prerequisite for the recruitment of circulating eosinophils. (Blood. 2000;95:263-269)

Allergens↗
PubMed2000

High-pressure suction drainage via a polyurethane foam in the management of poststernotomy mediastinitis.

BACKGROUND: This study was performed to evaluate the effectiveness of suction drainage in the management of early poststernotomy mediastinitis. METHODS: From September 1998 to August 1999, we encountered nine cases of poststernotomy mediastinitis out of 1,209 adult median sternotomies performed in this time period. All these cases were treated with suction drainage, which was recently introduced to our management protocol. From September 1997 to August 1998, we encountered 11 cases of poststernotomy mediastinitis of 1,343 adult median sternotomies. All these cases were initially treated by closed drainage and irrigation, which was our previous first-line management. We used the latter group as historical controls for the evaluation of suction drainage. Lengths of hospitalization were compared using the Mann-Whitney U test, and success versus failure of the primary treatment was compared using the chi2 test. RESULTS: Treatment with the suction dressing resulted in a decreased length of hospitalization after treatment starts (p = 0.02) and a lower rate of treatment failure (p = 0.03). CONCLUSIONS: The use of high-pressure suction drainage is a valuable adjunct in the early management of poststernotomy mediastinitis.

Aged↗
PubMed2000

Immunochemical studies on the putative plasmalemmal receptor for 1, 25-dihydroxyvitamin D(3). III. Vitamin D status.

The effect of vitamin D status on levels of the putative 1, 25(OH)(2)D(3) membrane receptor (pmVDR) was studied in chick intestine, kidney, and brain. Western analyses and assays for specific [(3)H]1,25(OH)(2)D(3) binding indicated that, in intestine, pmVDR levels were greatest in -D chicks relative to +1,25D and +D animals (P < 0.05). In kidney, protein levels and specific binding followed the order +D > +1,25D, -D. In brain, vitamin D status did not affect protein levels or specific binding levels. In tissue from normal chicks, both protein and specific binding followed the order of intestine > kidney > brain membranes. Intestinal cells were further evaluated for the effect of 1,25(OH)(2)D(3) on selected "rapid responses." Extrusion of (45)Ca in response to 130 pM 1, 25(OH)(2)D(3) in vitro was greater in cells from -D chicks than from +1,25D or normal birds. Analyses of signal transduction events revealed diminished hormone-induced intracellular calcium oscillations (as assessed by fura-2 fluorescence), and lack of steroid-enhanced protein kinase (PK) A activity in intestinal epithelial cells from -D chicks relative to +D chicks. PK C activation by 130 pM 1,25(OH)(2)D(3) was approximately twofold in cells from +D or -D chicks. The combined results indicate that vitamin D status differentially affects the pmVDR in intestine, kidney, and brain. In intestine, vitamin D deficiency differentially affects (45)Ca handling, intracellular calcium oscillations, PK A and PK C activities in response to 1,25(OH)(2)D(3).

Animals↗
PubMed2000

Expression of Meis and Pbx genes and their protein products in the developing telencephalon: implications for regional differentiation.

The Meis and Pbx genes encode for homeodomain proteins of the TALE class and have been shown to act as co-factors for other homeodomain transcription factors (Mann and Affolter, 1998. Curr. Opin. Genet. Dev. 8, 423-429). We have studied the expression of these genes in the mouse telencephalon and found that Meis1 and Meis2 display region-specific patterns of expression from embryonic day (E)10.5 until birth, defining distinct subterritories in the developing telencephalon. The expression of the Meis genes and their proteins is highest in the subventricular zone (SVZ) and mantle regions of the ventral telencephalon. Compared to the Meis genes, Pbx genes show a broader expression within the telencephalon. However, as is the case in Drosophila (Rieckhof et al., 1997. Cell 91, 171-183; Kurrant et al., 1998. Development 125, 1037-1048; Pai et al., 1998. Genes Dev. 12, 435-446), nuclear localized PBX proteins were found to correlate highly with Meis expression. In addition, DLX proteins co-localize with nuclear PBX in distinct regions of the ventral telencephalon.

Animals↗