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Biomedical subjects

K Carter

Publications and source records attributed to K Carter.

At least 37 records · Page 2Linked to original sources

A simple method of computing hip axis length using fan-beam densitometry and anthropometric measurements.

Hip axis length (HAL), a simple measure obtained from dual X-ray absorptiometry (DXA) scans of the proximal femur, predicts hip fracture, independent of bone mineral density and age. Owing to a magnification error associated with newer fan-beam DXA, automatic calculation of HAL, which is available in pencil-beam DXA, is inaccurate. The purpose of this study was to model HAL, measured from a pencil-beam DXA, as a function of HAL from a fan-beam DXA combined with other anthropometric measures. Proximal femur scans were performed using pencil- and fan-beam DXA in 21 women (ages 24-60). Height, weight, hip circumference, subject thickness, height of the greater trochanter and anterior superior iliac spine from the scanning table, and HAL as measured by a ruler from the scan printouts were recorded. Anthropometric measurements were taken by two researchers; all but the greater trochanter were reproducible (r > or = 0.92). A simple linear model using the manual measurement of HAL from the fan-beam scan, height, weight, body mass index, and hip circumference was able to predict HAL measured using the pencil-beam DXA with a high degree of accuracy (R(2) > or = 0.96). The fan-beam-acquired values of HAL using our model are nonbiased and accurate estimates of the "gold standard" pencil-beam method. This model may provide researchers and clinicians with a simple method of calculating HAL using fan-beam DXA.

Absorptiometry, Photon↗

Total neuropathy score: validation and reliability study.

OBJECTIVE: To determine the validity and reliability of the total neuropathy score (TNS) in normal subjects and in subjects with diabetic polyneuropathy. BACKGROUND: Clinical research in peripheral neuropathy requires validated outcome measures. Multiple outcome measures have been used in clinical trials, including symptom measures, functional scales, quantitative clinical examinations, nerve conduction studies, computerized sensory examinations, and nerve biopsy. Each of these measures has its strengths and weaknesses. In two previous studies of toxic neuropathy from chemotherapeutic agents, the authors used the TNS as the outcome measure. The TNS combines information obtained from grading of symptoms, signs, nerve conduction studies, and quantitative sensory tests, and provides a single measure to quantify neuropathy. METHODS: The authors measured the inter- and intrarater reliability of the TNS and preformed a cross-sectional validation study of the TNS and its subscales with the Mayo Clinic measures of neuropathy, neuropathy symptom score (NSS), and the neurologic impairment score (NIS) in five healthy control subjects and 30 individuals with varying severities of diabetic polyneuropathy. RESULTS: Inter- and intrarater reliability of the TNS was excellent (0.966 and 0.986 respectively). The cross-sectional validation study showed excellent correlations among all measures of neuropathy. CONCLUSIONS: The total neuropathy score is a validated measure of peripheral nerve function and could be used as an end point for clinical trials of peripheral neuropathy.

Adolescent↗

Efficacy of an ovine caseous lymphadenitis vaccine formulated using a genetically inactive form of the Corynebacterium pseudotuberculosis phospholipase D.

Caseous lymphadenitis (CLA) is an economically significant disease of sheep caused by the gram-positive bacterium Corynebacterium pseudotuberculosis. CLA vaccines are currently formulated using formalin inactivated culture supernatants that are rich in the C. pseudotuberculosis phospholipase D (PLD) exotoxin. One alternative to chemical detoxification is to inactivate the PLD genetically. This procedure not only provides a means to remove an onerous chemical treatment step but also the opportunity to increase gene expression, therefore improve protein yields. Using site-specific mutagenesis the C. pseudotuberculosis PLD was inactivated by substituting a serine residue at histidine 20 within the enzyme active site. CLA vaccine formulated using genetically inactivated PLD protected 44% of sheep against C. pseudotuberculosis challenge compared with 95% protection offered by the formalin inactivated preparation. Since there was no apparent difference in immune response mounted by vaccinated sheep the reason for this variation in vaccine efficacy remains unclear. Although genetic inactivation can be a convenient means to produce toxoid vaccines its use to develop a new CLA vaccine provided no net benefit over the conventional formulation.

Animals↗

Encounters with pharmaceutical sales representatives among practicing internists.

BACKGROUND: Although pharmaceutical sales representatives provide physicians with information on new products, these encounters have rarely been studied in practice settings. We examined these interactions among practicing internists and assessed whether prior residency policies limiting pharmaceutical sales representative access affected the subsequent behavior of practitioners. METHODS: We conducted a mail survey of the internal medicine staffs of a medical school hospital and two affiliated community hospitals. A second request was sent to nonresponders. After the second mailing, a random sample of nonresponders was compared with a similar sample of respondents. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression. RESULTS: Of the 346 (40%) internists who responded, 22% were women and 60% were trained in university hospitals. There were no differences in gender, subspecialization, or type of training when survey responders and nonresponders were compared. Two hundred eighty-seven (83%) physicians had met with pharmaceutical sales representatives within the previous year, of whom 248 (86%) had received drug samples. Having had a policy that limited access to pharmaceutical sales representatives during residency did not affect the subsequent likelihood of seeing these representatives (P = 0.20) or accepting samples in practice (P = 0.99). Those describing themselves as busy practitioners were significantly less likely to abstain from meeting pharmaceutical sales representatives (OR = 0.2, 95% CI: 0.1 to 0.6, P <0.001). Those with very frequent contacts (>10 times/month) were virtually all busy practitioners. CONCLUSIONS: Encounters between physicians and pharmaceutical sales representatives are common in internal medicine practice, especially in busy offices. Policies designed to limit pharmaceutical sales representative access during residency do not appear to affect the subsequent likelihood of meeting with pharmaceutical sales representatives or accepting samples.

Adult↗

Preliminary tests of a cognitive model of generalized anxiety disorder.

Although worry is the central feature of Generalised Anxiety Disorder (GAD), little is known about the factors that contribute to pathological or problematic worry. In a recent cognitive model of GAD, Wells, A. (1995) proposed that negative appraisal of worrying itself (meta-worry or type 2 worry) should be distinguished from other types of worrying (type 1 worry). A central feature of this model is the idea that individuals with GAD hold rigid positive beliefs about the usefulness of worrying as a coping strategy. However, these individuals also hold negative beliefs and appraise worrying as uncontrollable and dangerous. This combination of cognitions and associated responses leads to an increased frequency and generality of worrying, and thus to the pathological worry characteristic of GAD. This paper reports a preliminary test of the hypothesis that meta-worry contributes to problematic and pathological worrying, and this relationship is independent of the frequency of other types of worry. In testing for associations between worry dimensions we controlled for overlaps with Trait anxiety, and the controllability of worrying. Results of a series of regression analyses support the hypothesis that pathological worry is associated with meta-worry and this association is independent of Trait-anxiety and type 1 worry. The clinical implications of these data are briefly discussed.

Adult↗

A randomized trial of the effect of midazolam on intraocular pressure.

PURPOSE: The effect of midazolam on intraocular pressure (IOP) in adults was studied as an initial step in determining whether it can be used as a preoperative anxiolytic or sedative agent in children with glaucoma who are undergoing examination for IOP measurements. METHODS: This study followed a prospective, placebo controlled, randomized, double masked design. Fifty-five participants were enrolled after informed consent was obtained. Each enrolled patient underwent a brief history and eye examination. Measurements of IOP were taken at baseline and 5, 10, and 15 minutes after intravenous administration of 1 mg midazolam or placebo. IOP was the primary outcome measured. RESULTS: There was no difference in IOP fluctuation from baseline between patients who received midazolam and those who received placebo. CONCLUSION: Early results indicate that because midazolam does not lower IOP, it may be a useful adjunct to ketamine anesthesia in children with glaucoma undergoing ophthalmologic examination under anesthesia. However, studies of midazolam must be conducted in children and patients with glaucoma before its use in these populations can be recommended.

Anesthesia, Intravenous↗

LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon gamma (IFNgamma) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin beta receptor (LTbetaR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTbetaR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTbetaR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8(+) TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNgamma. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.

Apoptosis↗

Phacoemulsification and lens implantation in patients treated with aspirin or warfarin.

PURPOSE: To determine the incidence and nature of hemorrhagic complications in patients having phacoemulsification and foldable intraocular lens (IOL) implantation while taking aspirin or warfarin. SETTING: The Jules Stein Eye Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA. METHODS: This retrospective study reviewed the charts from the practice of 1 ophthalmic surgeon. The type of medication, dosage, indication for anticoagulant therapy, type of incision, type of anesthesia, and intraoperative and postoperative hemorrhagic complications were recorded. RESULTS: Sixty-two patients (82 eyes) taking aspirin and 25 patients (31 eyes) taking warfarin were identified. Seven eyes in the aspirin group (8.5%) and 3 in the warfarin group (9.7%) experienced subconjunctival hemorrhages. Eight of the 10 subconjunctival hemorrhages occurred in eyes with scleral incisions. The remaining 2 occurred in eyes with corneal incisions. No eye developed lid ecchymosis, retrobulbar hemorrhage, hyphema, or suprachoroidal hemorrhage. CONCLUSIONS: Phacoemulsification with foldable IOL implantation was performed safely in patients taking aspirin or warfarin. Subconjunctival hemorrhage was the most common hemorrhagic complication.

Anticoagulants↗

Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations.

The predicted mutability profile (MUTPRED) of the phenylalanine hydroxylase (PAH) gene shows that the 48 CpG sites (template and atemplate strands) are either empty of known mutations (7 sites), harbour "PKU" alleles involving CpG doublets (16 sites), or contain mutations that do not involve a C-->T or G-->A substitution in the doublet. These hypermutable sites harbour 32 different mutations in association with at least 66 different haplotypes and hyperphenylalaninemia. The E280K mutation in exon 7 of the PAH gene is a cause of phenylketonuria. It occurs on four different haplotypes in Europeans and on haplotypes 1 and 2 in Quebec. Whereas a single recombination event could explain the two haplotype associations in Quebec, the mutation does involve a CpG dinucleotide. By analyzing multiallelic markers 5' (STR) and 3' (VNTR) to the E280K allele on 12 mutant and 30 normal chromosomes, we conclude that recurrent mutation is the likely origin of E280K in Quebec. The PAH mutation database shows that the allele accounts for 1.5% of PKU chromosomes worldwide.

Codon↗

Oral botryomycosis: a case report.

We present a 42-year-old male with botryomycosis initially presenting with left-sided proptosis due to an infraorbital mass. A biopsy through an anterior orbitotomy yielded indeterminate histopathology. The patient later developed a similar oral lesion which was biopsied and found to be botryomycosis. The oral lesion recurred after initial surgical treatment, but responded to antibiotic therapy. Discussion of this case along with a review of the literature is presented to offer guidelines for recognition and management of this rare disorder.

Adult↗

Analysis of phenylalanine hydroxylase genotypes and hyperphenylalaninemia phenotypes using L-[1-13C]phenylalanine oxidation rates in vivo: a pilot study.

Hyperphenylalaninemia (HPA) resulting from deficient activity of phenylalanine hydroxylase (PAH) is caused by mutations in the human PAH gene (McKusick 261600). Herein, we report a noninvasive method to: 1) estimate whole-body phenylalanine oxidation in patients with HPA and 2) compare effects of mutant genotypes on phenotypes. We used oral L-[1-13C]phenylalanine as a substrate and measured 13CO2 formation in the first hour as an index of phenylalanine oxidation rates in: 1) patients with PKU (n = 6), variant phenylketonuria (PKU) (n = 7) and non-PKU HPA (n = 4); 2) obligate heterozygotes (n = 18); and 3) controls (n = 8). PAH mutations were identified by PCR, denaturing gradient gel electrophoresis, and DNA sequencing. Phenylalanine oxidation rates demonstrated a gene dosage effect; oxidation in heterozygotes was intermediate between probands and controls. The three classes of HPA had different mean oxidation rates (PKU < variant PKU < non-PKU HPA). The in vivo phenotype (HPA class or whole-body oxidation rate) did not always correspond to prediction from in vitro expression analysis of the mutation effect on enzyme activity. The findings indicate that the in vivo metrical trait (phenylalanine oxidation rate) is not a simple equivalent of phenylalanine hydroxylation activity (unit of protein phenotype) and, as expected, is an emergent property under the control of more than the PAH locus.

Adolescent↗

Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination.

Three distinct DNA ligases, I to III, have been found previously in mammalian cells, but a cloned cDNA has been identified only for DNA ligase I, an essential enzyme active in DNA replication. A short peptide sequence conserved close to the C terminus of all known eukaryotic DNA ligases was used to search for additional homologous sequences in human cDNA libraries. Two different incomplete cDNA clones that showed partial homology to the conserved peptide were identified. Full-length cDNAs were obtained and expressed by in vitro transcription and translation. The 103-kDa product of one cDNA clone formed a characteristic complex with the XRCC1 DNA repair protein and was identical with the previously described DNA ligase III. DNA ligase III appears closely related to the smaller DNA ligase II. The 96-kDa in vitro translation product of the second cDNA clone was also shown to be an ATP-dependent DNA ligase. A fourth DNA ligase (DNA ligase IV) has been purified from human cells and shown to be identical to the 96-kDa DNA ligase by unique agreement between mass spectrometry data on tryptic peptides from the purified enzyme and the predicted open reading frame of the cloned cDNA. The amino acid sequences of DNA ligases III and IV share a related active-site motif and several short regions of homology with DNA ligase I, other DNA ligases, and RNA capping enzymes. DNA ligases III and IV are encoded by distinct genes located on human chromosomes 17q11.2-12 and 13q33-34, respectively.

Amino Acid Sequence↗

Gastric syphilis mimicking linitis plastica.

The decreased incidence of gastric syphilis has made its clinical presentation less widely appreciated. A 61-year-old man suffering from epigastric pain, nausea, and vomiting had an initial diagnosis of gastric carcinoma; the pathologic diagnosis was equivocal. Eventually, gastric syphilis was diagnosed. In the context of the case described below, positive serologic findings in a relatively young adult should raise the suspicion of gastric syphilis. Carcinoma must be ruled out, lest the patient lose valuable time while being treated for syphilis.

Biopsy↗

Restitution of frog gastric mucosa in vitro: effect of basic fibroblast growth factor.

BACKGROUND: Rapid re-epithelialization after superficial gastric mucosal injury is caused by migration of persisting viable epithelial cells. Basic fibroblast growth factor (bFGF) has been reported to enhance the healing of experimental duodenal ulcer, but its mode of action is unclear. The present experiments examine whether an effect of bFGF on restitution might contribute to such healing. METHODS: Paired halves of bullfrog fundic gastric mucosa in Ussing chambers were injured by luminal exposure to 1 mol/L NaCl for 10 minutes. RESULTS: Luminal protamine or suramin, both known to interfere with endogenous bFGF, significantly inhibited electrophysiological recovery at neutral luminal pH (pHL). Luminal sucrose octasulfate, which prevents acid degradation of bFGF, and an exogenous, acid-resistant form of bFGF allowed electrophysiological recovery at a pHL of 3.0 that completely prevented restitution in control tissues. Electrophysiological recovery correlated well with morphological restitution. The presence of endogenous bFGF in normal and restituting bullfrog mucosa was confirmed by positive staining with a monoclonal antibody. CONCLUSIONS: It is concluded that rapid epithelial repair after surface injury is at least in part mediated by bFGF.

Animals↗

Role of electric stimulation in bladder evacuation following spinal cord transection.

Neural stimulation is potentially a valuable therapeutic tool in the treatment of neurogenic bladder with detrusor areflexia. We studied 20 dogs in different groups, up to eight months, and compared the effect of electric stimulation with intermittent catheterization, specially during spinal shock phase. We found that early stimulation hastened the return of detrusor activity. When stimulation was delayed, the bladder could still regain its activity, and when the pace-maker was turned off, the detrusor activity was gradually decreased. Neurostimulation can completely empty bladder up to eight months. The lowest A.Ch. content in detrusor muscle was found in intermittent catheterization group and in this group the detrusor strips showed marked supersensitivity to urecholine stimulation than the bladders managed by electric stimulation. Also, we found that electric stimulation reduced the complications caused by intermittent catheterization and protected kidney function.

Animals↗