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K M Morrison

Publications and source records attributed to K M Morrison.

12 recordsLinked to original sources
PubMed2005

Fetal and neonatal exposure to nicotine in Wistar rats results in increased beta cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes.

AIMS/HYPOTHESIS: Epidemiological studies report an increased risk of obesity and type 2 diabetes in children born to women who smoked during pregnancy. This study examines the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarettes, on postnatal growth, adiposity and glucose homeostasis. METHODS: Female Wistar rats were given either saline (vehicle) or nicotine (1 mg kg(-1) day(-1)) during pregnancy and lactation. Serum and pancreas tissue were collected from the infant rats at birth. Postnatal growth was assessed weekly until the rats reached 26 weeks of age and glucose homeostasis was examined by OGTTs performed at 7 and 26 weeks of age. RESULTS: Exposure to nicotine resulted in increased postnatal growth and adiposity. Nicotine exposure also resulted in dysglycaemia at 7 and 26 weeks of age. Serum insulin concentrations were decreased in the pups exposed to nicotine at birth. This was associated with increased beta cell apoptosis (pups of saline-treated mothers 8.8+/-1.21% apoptotic beta cells; pups of nicotine-treated mothers 27.8+/-3.1% apoptotic beta cells). CONCLUSIONS/INTERPRETATION: Fetal and neonatal exposure to nicotine results in metabolic changes in the offspring that are consistent with obesity and type 2 diabetes. We propose that these metabolic changes may be a consequence of the initial insult to the beta cell during fetal life and that this animal model has many characteristics of diabetes in humans.

Adiposity↗
PubMed2001

Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat sequences can be excluded.

Acromegaly↗
PubMed2001

Weight loss at high altitude.

Loss of appetite and weight are frequently observed at altitudes above 5000 m. However, the pathophysiology behind changes in body composition at extreme altitude is still not fully understood. Proper acclimatization to altitude and high caloric intake minimizes, but can not completely prevent significant weight loss under the influence of hypobaric hypoxia. The discovery of leptin in 1994 has initiated a new research area investigating molecular networks that connect peripheral organs with the central nervous system to sense and regulate energy intake as well as energy expenditure. Since then, a whole microcosm of new hormones, neurotransmitters and receptors has been discovered and studied with respect to body weight control. Those agents include neuropeptide Y (NPY), agouti-related protein (AGRP), melanocortin receptors (MC-R), cocaine-amphetamine regulated transcript (CART), pro-opiomelanocortin (POMC), orexin A and B (hypocretins), melanin-concentrating hormone (MCH) and ghrelin (endogenous ligand of the growth hormone secretagogue receptor). This overview will introduce the current concepts of the molecular control of energy homeostasis and attempt to reexamine the effects of altitude on appetite and body composition in light of these concepts. An overview of studies on changes of appetite and body composition at high altitude will be followed by the presentation of recent data on changes of endocrine parameters at hypobaric hypoxia that could be involved in the pathophysiology of weight loss.

Altitude↗
PubMed2001

Findings and theoretical considerations on the usefulness of the acid-labile subunit in the monitoring of acromegaly.

Growth hormone (GH) action induces a variety of biochemical factors of which insulin-like growth factor I (IGF-I) is conventionally measured for the diagnosis and monitoring of GH-related disorders such as GH deficiency or acromegaly. IGF-I circulates predominantly as a ternary complex with IGF-binding protein 3 (IGFBP-3) and the acid labile subunit (ALS). In the treatment of active acromegaly with the GH receptor antagonist pegvisomant, ALS showed a closer correlation with the change in ring size, measured as a clinical indicator of disease activity, than did IGF-I or IGFBP-3. ALS thus seems to be a clinically useful marker of disease activity in acromegaly.

Acromegaly↗
PubMed2001

Normal values of insulin-like growth factor I and their clinical utility in adults.

The concentration of circulating insulin-like growth factor I (IGF-I) is a potential marker for growth hormone (GH) deficiency in adults. Indeed, researchers have shown that IGF-I levels are of greater diagnostic value than other possible markers, such as IGF-binding protein 3 (IGFBP-3) and the acid-labile subunit (ALS). Accurate age-matched normative data are essential to give patient data diagnostic meaning. Such data are assay specific and must exclude those individuals with certain confounding medical conditions. Post-diagnosis, monitoring of IGF-I and IGFBP-3 levels can be used to assess the efficacy and safety of GH replacement therapy. Furthermore, IGF-I levels, and possibly ALS levels, can be used to aid the diagnosis and monitoring of acromegaly. For example, acromegaly can be excluded in patients with normal IGF-I levels if liver failure and malnutrition/malabsorption are ruled out.

Acromegaly↗
PubMed2000

The application of arthroscopic principles to bone grafting of delayed union of long bone fractures.

The purpose of this study was to explore the potential of applying arthroscopic techniques to autogenous bone grafting of long bone fracture delayed union. There were 9 patients in this initial series, including 4 patients (average age, 37 years) with humeral lesions and 5 patients (average age, 25 years) with tibial fractures. There were 6 men and 3 women. Techniques customarily employed in arthroscopy were used to visualize, expose, and deliver the onlay cancellous bone grafts. Bony union occurred in all but 1 patient in an average of 4 months. This patient had a fibrous union and sustained a reinjury that led to successful repeat open bone graft surgery. The arthroscopic approach for bone grafting of certain long bone delayed union appears to be a safe and effective procedure. The procedure is best suited for patients with mechanically stabilized fragments, and it lends itself to those with overlying skin or soft tissue compromise. There are some relative contraindications: grossly unstable fragments, severe malunion, and/or infection.

Adolescent↗
PubMed2000

Effects of growth hormone replacement therapy on levels of cortisol and cortisol-binding globulin in hypopituitary adults.

OBJECTIVE: To determine if human growth hormone (hGH) replacement therapy alters pharmacokinetics of hydrocortisone (CS) substitution in hypopituitary adults. DESIGN: To this aim, we analysed serum and salivary CS profiles 270 min after oral CS administration at baseline and 6 and 12 months after initiation of hGH replacement therapy. METHODS: Serum IGF-I, cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG) and sex hormone-binding hormone (SHBG) were measured using commercially available radioimmunoassays. In-house immunofluorometric assays were employed for measurements of CS and hGH. RESULTS: hGH replacement did not change total serum CS bioavailability (area under the serum cortisol profile curve). Interference of orally administered CS with salivary measurement of free CS (fCS) caused significant bias. Therefore, fCS levels were calculated from their total CS and cortisol-binding globulin (CBG) levels. CBG decreased by approximately 30% after both 6 and 12 months of hGH replacement therapy (n=20, P<0.01). A significant negative correlation between deltaCBG (CBG6months-CBGbaseline) and deltaIGF-I (IGF-I6months-IGF-Ibaseline) was observed (P=0.04). The calculated values of free CS tended to increase with physiological hGH replacement, but this effect was marginal and did not reach statistical significance. In contrast to the CBG concentrations, plasma levels of sex hormone-binding globulin and thyroxine-binding globulin were essentially stable. CONCLUSION: Given that no clinically relevant alterations in pharmacokinetics of CS were evoked by initiation of hGH replacement in hypopituitary adults, we conclude that CS substitution does not require dose adjustment after initiation of hGH replacement.

Adult↗
PubMed1994

Severe occupational traumatic injuries.

Severe occupational traumatic injuries represent a challenge to workers and physicians. Efforts to prevent occupational injuries, such as education, protective equipment, adherence to safety procedures, and personal responsibility, are of critical importance. The physician's role as educator, consultant, and on-site manager of these injuries forms the basis for effective management of severe occupational traumatic injuries. Rapid assessment and treatment by coworkers trained in first aid can be vital in preventing more serious sequelae.

Accidents, Occupational↗
PubMed1993

A cosmid library specific for human chromosome regions 6p21.3 and 6q27.

We have explored the potential of irradiation-fusion gene transfer (IFGT) hybrids as a source of well-defined human chromosome fragments from which probes can be derived. Extensive characterization of the IFGT hybrid 4J4 with a full panel of markers from Chromosome (Chr) 6 showed that the human DNA content derives largely from 6p21.3 and 6q27. A cosmid library has been constructed from 4J4 DNA, and 370 recombinants containing human DNA have been isolated and overlapping clones ordered into 20 contigs. Regional localization of representative clones from each contig, determined by fluorescent in situ hybridization (FISH), places 13 contigs in 6q27 and 6 in 6p21.3. Preliminary screening of cDNA libraries with selected cosmids has identified two expressed sequences. Since there are a number of medically important genes in both these regions of human Chr 6 with several disease loci linked to the HLA-A region in 6p21.3 and various tumor suppressor genes to 6q27, this library will provide a valuable resource to aid the isolation of candidate genes for these diseases. In addition, unique markers for detailed physical and genetic mapping of these regions of human Chr 6 can be easily obtained.

Base Sequence↗
PubMed1991

Plating of the fibula. Its potential value as an adjunct to external fixation of the tibia.

There is added stability when plate fixation of the fibula supplements the external fixator used in treating tibial fractures associated with a segmental defect. An anatomic specimen model of a Grade III open fracture of the tibia with an associated fibular fracture was used in this study. Fibular internal fixation using an AO standard plate was performed on one of each of five matched pairs of legs. These were then subjected to identical loads in compression and torsion. The numeric values obtained during loading in all modes were converted to ratios between each of the tested pair to directly compare the effect of stabilization of the fibula. The final results showed that in each case, the preparation with fibular plating had improved resistance to deformation in axial loading. On average, the plated specimens were 2.2 times stiffer. In torsion, plating the fibula did not appear to affect the resistance of the construct to the applied load. Supplemental plate fixation of the fibula in fractures of the tibia with segmental defects may improve subsequent morbidity. The increased rigidity of the system may be sufficient to allow partial to full weight bearing immediately after surgery. This may have significant value in the management of the polytraumatized patient.

Biomechanical Phenomena↗
PubMed1989

"Interventional angiography." A possible role in intraoperative balloon occlusion catheterization of lacerated pelvic arteries.

The use of interventional angiography has been limited in the past to the angiography suite. Significant technical difficulties have been associated with transfer of the unstable patient from the operating room for this procedure. However, current radiographic sophistication now exists to allow rapid intraoperative digital subtraction angiography of uncompromised quality to be performed. An animal model using these techniques is presented.

Angiography↗