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Biomedical subjects

C Larson

Publications and source records attributed to C Larson.

At least 19 recordsLinked to original sources

Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects.

We report two infants identified by tandem mass spectrometry (MS/MS) of neonatal blood spot acylcarnitines and confirmed by molecular genetic analysis to have long-chain fatty acid oxidation defects. In both cases, acylcarnitine concentrations in confirmatory plasma samples were normal. None the less, molecular testing identified trifunctional protein (TFP) deficiency (McKusick 600890) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (McKusick 201475).

Acyl-CoA Dehydrogenase, Long-Chain↗

Identification of a missense mutation (G329A;Arg(110)--> GLN) in the human FUT7 gene.

The human FUT7 gene codes for the alpha1,3-fucosyltransferase VII (Fuc-TVII), which is involved in the biosynthesis of the sialyl Lewis x (SLe(x)) epitope on human leukocytes. The FUT7 gene has so far been considered to be monomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by Western blot analysis using monoclonal antibodies directed against SLe(x) and SLe(x)-related epitopes. One individual showed lower levels of SLe(x) expression and an elevated expression of CD65s compared to controls. The coding regions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg(110) --> Gln) was found in one allele, whereas the other FUT7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 cells transiently transfected with the mutated FUT7 construct. The FUT7 Arg(110) is conserved in all previously cloned vertebrate alpha 1,3-fucosyltransferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of < or =1% for this mutation was found (3 heterozygotes). Genetic characterization of the family members of one of the additional heterozygotes identified one individual carrying the G329A mutation in both FUT7 alleles. Peripheral blood neutrophils of this homozygously mutated individual showed a lowered expression of SLe(x) and an elevated expression of CD65s when analyzed by Western blot and flow cytometry. The homozygous individual was diagnosed with ulcer disease, non-insulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome but had no history of recurrent bacterial infections or leukocytosis.

Animals↗

Expression of human prostatic acid phosphatase gene is regulated by upstream negative and positive elements.

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. To understand the regulation of expression of the PAcP gene, we studied the cis-regulatory elements of its promoter. A DNA fragment from -2899 to +87 base pairs (bp) of PAcP gene was fused to the chloramphenicol acetyltransferase (CAT) reporter gene and introduced into PC-3 and LNCaP human prostate cancer cells. The expression of the CAT gene driven by the PAcP promoter was assessed in transient expression assays. Sequential 5' deletions of the promoter were constructed and analyzed to reveal the positive and the negative regulatory elements that are involved in regulating the transcription of the PAcP gene. Our data showed that the proximal sequence -1305/+87 bp directs a high level of the CAT activity in both cell lines. Deletion of the region from -1305 to -779 resulted in approximately a 10- and three-fold decrease of the PAcP promoter activity in PC-3 and LNCaP cells, respectively. Interestingly, an inverse correlation of the CAT activity with the cell growth was observed when the reporter gene was driven by the -1305/+87 fragment, but not by the -779/+87 fragment. Two regions of transcriptional suppression were identified and located in positions from -2899 to -2583, and from -2583 to -1305 bp. Furthermore, the activity of the core promoter region from -779 to +87 bp can be activated by a SV-40 enhancer. The results, thus, clearly demonstrate the presence of positive and negative cis-elements in the promoter region of the PAcP gene.

Acid Phosphatase↗

Nature, incidence, and cause of work-related amputations in Minnesota.

BACKGROUND: The Minnesota Sentinel Event Notification System for Occupational Risks (SENSOR) has collected data on the nature, incidence, and cause of work-related amputation injuries that have taken place since 1992. METHODS: SENSOR defined an amputation as any finger amputation or the loss of any other body part; 832 workers were identified as having amputation injuries between 1994 and 1995 and 72% of these workers completed telephone interviews. RESULTS: The amputation injury rate for Minnesota workers was 39 per 100,000 workers, with agriculture and manufacturing having the highest rates. Sixty-six percent of the injuries involved one finger; 14% involved two or more fingers. Persons working with machinery reported 73% of the injuries. CONCLUSIONS: A closer examination of the incidence and causes for amputation injuries shows that these were not random events. Reliance on human reactions to prevent injury is inadequate; therefore, additional research needs to be conducted.

Accidents, Occupational↗

Medical, personal, and occupational outcomes for work-related amputations in Minnesota.

BACKGROUND: The Minnesota Sentinel Event Notification System for Occupational Risks (SENSOR) surveillance system has collected data on the medical, personal, and occupational outcomes associated with work-related amputations since 1992. METHODS: SENSOR defined amputations as any finger amputation or the loss of any other body part; 832 workers were identified as having amputation injuries between 1994 and 1995 and 72% of these workers completed a telephone interview. RESULTS: Twenty percent of those injured required overnight hospitalization. Ninety-one percent of the cases reported having missed work, with 56% reporting missing ten or more days. Individuals working on their usual jobs at the time of injury were more likely to report less serious medical and occupational outcomes. CONCLUSIONS: Severe injuries were significantly associated with worse medical, personal, and occupational outcomes. Two groups of machines, material handling, and powered handtools were associated with a higher proportion of severe injuries.

Absenteeism↗

Experimental studies of extinction dynamics

Extinction of populations occurs naturally, but global extinction rates are accelerating, making understanding extinction a high priority for conservation. Extinction in experimental populations of brine shrimp (Artemia franciscana) was measured to assess hypothesized extinction processes. Greater initial population size, greater maximum population size supported by the environment, and lower variation in environmental conditions reduced the likelihood of extinction, as hypothesized. However, initial population size was less important, and maximum population size and environmental variation were more important than often hypothesized. Unexpectedly, deterministic oscillations in population size due to inherent nonlinear dynamics and overcrowding were as important or more important than hypothesized processes.

Journal Article↗

Mechanical load stimulates expression of novel genes in vivo and in vitro in avian flexor tendon cells.

OBJECTIVE: Our experiments were designed to test the hypothesis that tendon cells might respond differently to applied strain in vitro than in vivo. DESIGN: We tested cells in whole tendons from exercised chickens and from isolated surface (TSC) and internal tendon (TIF) in vitro that were subjected to mechanical strain. We hypothesized that tendon cells differentially express genes in response to mechanical loading in vivo and in vitro. METHODS: We utilized an in-vivo exercise model in which chickens were run on a treadmill in an acute loading regime for 1 h 45 min with the balance of time at rest to 6 h total time. Gene expression was analyzed by a differential display technique. In addition, isolated avian flexor digitorum profundus TSC and TIF cells were subjected to cyclic stretching at 1 Hz, 5% average elongation for 6 h, +/- PDGF-BB, IGF-I, TGF-beta 1, PTH, estrogen, PGE2, or no drug and/or no load. mRNA was then collected and samples were subjected to differential display analysis. CONCLUSIONS: Load with or without growth factor and hormone treatments induced expression of novel genes as well as some known genes that were novel to tendon cells. We conclude that the study of gene expression in mechanically loaded cells in vivo and in vitro will lead to the discovery of novel and important marker proteins that may yield clues to positive and negative cell strain responses that are protective under one set of conditions and destructive under another.

Animals↗

Perceived barriers to childhood immunization: a physician and parent survey in a southeastern urban/rural community.

PURPOSE: To identify physicians' and parents' perceptions of barriers to completing the immunization process by age 24 months. METHODS: A questionnaire hand-delivered to 110 physicians who treat children yielded a response rate of 83%. A telephone survey conducted with parents of a random sample of 2,100 children younger than three years of age selected from the county birth records yielded an adjusted response rate of 87%. RESULTS: Physicians' response fell into two categories: those with more and less than 90% up-to-date immunizations. Those with less than 90% indicated that parental knowledge is the primary reason. Those with more than 90% reported telephone follow-up for missed appointments. The top three barriers reported by parents; (1) waiting time at the clinic (33%), (2) child too ill at time of appointment (21%), and (3) insurance does not cover immunizations (16%). CONCLUSIONS: There is an opportunity for education intervention with physicians, policy makers, and parents in several key areas: (1) fact-based contraindications to immunizations, (2) effective means of follow-up, (3) accessibility to immunization for the under-insured, and (4) parental responsibility.

Child, Preschool↗

Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys.

The authors examined the hypothesis that rhesus monkeys with extreme right frontal electroencephalographic activity would have higher cortisol levels and would be more fearful compared with monkeys with extreme left frontal activity. The authors first showed that individual differences in asymmetric frontal electrical activity are a stable characteristic. Next, the authors demonstrated that relative right asymmetric frontal activity and cortisol levels are correlated in animals 1 year of age. Additionally, extreme right frontal animals had elevated cortisol concentrations and more intense defensive responses. At 3 years of age, extreme right frontal animals continued to have elevated cortisol concentrations. These findings demonstrate important relations among extreme asymmetric frontal electrical activity, cortisol levels, and trait-like fear-related behaviors in young rhesus monkeys.

Agonistic Behavior↗

Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation.

PKD1 is the most common site for mutations in human autosomal dominant polycystic kidney disease (ADPKD). ADPKD is characterized by progressive replacement of kidney tissue by epithelial cysts and eventual renal failure. Hepatic and pancreatic cysts are also common. The PKD1 protein, polycystin, is a cell-surface protein of unknown function that is widely expressed in epithelia and in vascular smooth muscle and myocardium. None of the genetic forms of murine polycystic disease map to the murine Pkd1 locus. We introduced into mice by homologous recombination a Pkd1 truncation mutation, Pkd1-, that mimics a mutation found in ADPKD. Pkd1- heterozygotes have no discernible phenotype, whereas homozygotes die during the perinatal period with massively enlarged cystic kidneys, pancreatic ductal cysts and pulmonary hypoplasia. Renal cyst formation begins at embryonic day 15.5 (E15.5) in proximal tubules and progresses rapidly to replace the entire renal parenchyma. The timing of cyst formation indicates that full-length polycystin is required for normal morphogenesis during elongation and maturation of tubular structures in the kidney and pancreas.

Abnormalities, Multiple↗

Decision making errors in the use of interlocking tibial nails.

Seventy-one fractures of the tibial shaft were treated with interlocking intramedullary nails. None of the fractures were treated with static locking of the intramedullary nails. These 71 fractures were studied to determine whether certain fracture patterns are prone to loss of alignment when static interlocking is not used. Loss of alignment was defined as shortening of 1 cm or more and/or change in angulation of at least 5 degrees. Loss of alignment occurred in eight of the 71 (11%) fractures. Shortening and/or angulation occurred in seven of 22 spiral and short oblique fractures, and in none of 27 transverse fracture patterns. It was concluded that the dynamically locked and nonlocked modes of intramedullary nailing should not be used in the stabilization of spiral and oblique fractures of the tibial shaft.

Adolescent↗

Bioavailability and efficacy of omeprazole given orally and by nasogastric tube.

We compared the bioavailability and the efficacy of omeprazole provided either as encapsulated enteric-coated granules or as enteric-coated granules delivered via a nasogastric tube in 10 healthy subjects. Omeprazole reduced mean pentagastrin-stimulated peak gastric acid secretion by 85.5% +/- 23.7% when delivered orally and by 79.6% +/- 32.1% when delivered by nasogastric tube; the mean plasma omeprazole concentration area under the curve (AUC) was 2.02 +/- 0.79 after oral delivery and 1.74 +/- 1.89 after nasogastric tube delivery. There was no significant difference in these parameters between the two routes of administration, and there was excellent intrasubject correlating between oral and nasogastric percent acid suppression and AUC. There was a close correlation between AUC and percent acid suppression at AUC values below 0.6, and complete acid suppression at AUC values above 0.6, regardless of the delivery route. We conclude that omeprazole delivered as enteric-coated granules via nasogastric tube provides equal bioavailability and gastric acid suppression as omeprazole given orally in its proprietary formulation.

Administration, Oral↗

Comparing outcomes and charges for patients with acute myocardial infarction in three community hospitals: an approach for assessing "value".

OBJECTIVE: To assess the value of care (i.e. outcomes in relation to charges) for acute myocardial infarction (Acute MI) patients in three community hospitals after controlling for patient mix differences. DESIGN: An observational study of a cohort of acute MI patients admitted to hospital for care were studied based on medical record review and on patient-completed questionnaires at 8 weeks post-discharge. SETTING: Three community hospitals located in urban areas in the southeastern region of the United States. PATIENTS: A consecutive sample of 133 non-transfer Acute MI patients were entered into the study based on EKG results, enzyme tests and chest pain characteristics. Hospital medical record and charge data were available on all patients and patient-reports on 86% of survivors. MAIN OUTCOME MEASURES: Data were gathered on clinical outcomes (death, angina, dyspnea), functional outcomes (physical and psychosocial), satisfaction, and resource intensity (length of stay, total hospital charges, ancillary charges). Because of patient mix differences across hospitals, outcomes were adjusted for severity of Acute MI, comorbidity and demographics. RESULTS: There were important patient mix differences across hospitals. For example, Hospital C had more comorbidity than Hospital B (57.78% of Hospital C patients vs 15.00% of Hospital B patients were rated moderate or severe using a well tested index, p < 0.0001). After adjusting for patient mix differences, Hospital C scored significantly better on four of six outcome measures (i.e. angina, dyspnea, physical functioning, psychosocial functioning). For example, Hospital C's patients' mean scores on physical functioning at 8 week follow-up averaged 75.19 (on a 0-100 scale), while Hospital A's was 63.03 and Hospital B's was 48.57 (F-ratio = 4.95; p < 0.05). However, Hospital A scored significantly lower on all three resource intensity indicators (length of stay, ancillary charges, and total charges). For example, Hospital A's ancillary charges averaged $10,752 while Hospital B's and C's averaged $11,432 and $16,598 respectively. Between-hospital comparisons on adjusted mortality and satisfaction did not differ significantly. CONCLUSION: The "value" profiles (i.e. outcomes related to charges) produced by these three hospitals were substantially different. Studies that simultaneously measure outcomes, costs, patient mix and processes have potential to: (a) enable clinical teams to improve the measurable value of clinical care; and (b) enable purchasers to better evaluate which providers to select as preferred sources of care.

Acute Disease↗

Physiology of oropharyngeal swallow in the cat: a videofluoroscopic and electromyographic study.

The majority of animal studies of deglutition have examined electrically stimulated swallows in sedated animals. This present investigation examined oropharyngeal and cervical esophageal swallow physiology in three awake normal domestic cats using concurrent electromyography (EMG) and videofluorography (VFG). Hooked wire electrodes were surgically implanted into six oropharyngeal muscles in each cat. During collection of VFG and EMG data, each cat ate barium-impregnated cat food while the fluorography tube focused on a lateral view of the oral cavity, pharynx, and cervical esophagus. A number of significant differences in the physiology of swallowing were found between the cat and human adult. The oral stage of swallow is much longer in the cat with bolus accumulation in the valleculae. Duration and components of the pharyngeal stage of swallow are much faster, and the pharyngeal stage occurs earlier in relation to bolus passage through the cricopharyngeus. In addition, the cat exhibits a marked superior constrictor bulge at the onset of the pharyngeal contractile wave and summation of the peristaltic waves in the esophagus, whereas the human adult does not. Feline swallow physiology is more similar to that of the human infant than that of human adults.

Animals↗

A randomized community trial of prepackaged and homemade oral rehydration therapies.

OBJECTIVE: To compare the effectiveness of prepackaged oral rehydration solutions with homemade cereal-based oral rehydration therapy in the treatment of acute childhood diarrhea in children younger than 5 years. BACKGROUND: In Ethiopia, approximately 40% of all mortality in children younger than 5 years, or over 200,000 annual deaths, is attributable to acute childhood diarrhea. Less than 15% of the episodes of acute childhood diarrhea are treated with oral rehydration solutions. SUBJECTS: Two hundred ninety-one children younger than 5 years with acute childhood diarrhea. METHODS: A randomized field trial comparing the effectiveness of an entirely homemade cereal-based oral rehydration therapy (HC-ORT, n = 103) with two alternative prepackaged salt solutions, a glucose-based oral rehydration solution (G-ORS, n = 98) and a cereal-based oral rehydration solution (C-ORS, n = 90), in the treatment of mild to moderate acute childhood diarrhea in children younger than 5 years. RESULTS: Subjects in the HC-ORT group demonstrated equivalent or better weight gain than those in the C-ORS or G-ORS groups at 24, 48, 72, and 96 hours following the onset of treatment. The beneficial weight-gain effect of HC-ORT was most pronounced in infants younger than 12 months, following adjustment for demographic and baseline clinical characteristics. Compliance with ORT use through 96 hours was significantly better among caretakers of children receiving HC-ORT. Minor errors in the preparation of these oral rehydration regimens occurred more frequently among caretakers preparing either of the cereal-based ones. CONCLUSIONS: That HC-ORT is an effective, culturally more acceptable alternative to G-ORS or C-ORS. The implementation of well-monitored, community-based HC-ORT programs in less developed countries is recommended.

Acute Disease↗

Viscosity effects on EMG activity in normal swallow.

This study investigated the effects of six consistencies on measures of swallow duration, muscle activity, and sound. Electromyographic (EMG) recordings of the submental and infrahyoid muscle complexes, and audio recordings of neck sounds were made while 5 normal subjects swallowed two foods in each of three consistency categories: liquid, thin paste, and thick paste. Total swallow duration, measured from EMG, increased significantly across consistency categories from liquids to thin pastes to thick pastes. Liquids and thin pastes were significantly different from thick pastes on all but one EMG measure. However, liquids and thin pastes failed to reach significance on any of the EMG measures. EMG activity in the submental muscles most often initiated the swallow whereas the infrahyoid muscle activity most frequently terminated the swallow. A sound spike occurred at relatively the same time in each swallow. Results are discussed in terms of systematic modulations of muscle activity during swallow.

Adult↗

The health consequences of intrauterine growth retardation in southwestern Ethiopia.

Although over 90% of low birth weight deliveries occur in the developing world, knowledge of its occurrence and consequences are largely based on studies in developed populations. The aim of this investigation was to determine the health consequences of intrauterine growth retardation (IUGR) among an historical cohort of children delivered in a regional hospital located in southwestern Ethiopia. Following a census of all births over a three year period 116 full-term, IUGR and normal birth weight (NBW) matched pairs between 3 and 40 months of age were identified. IUGR children were found to be at elevated risk for moderate to severe malnutrition [relative risk (RR) = 2.26 (1.15,4.43)], frequent illnesses (RR = 1.29 (1.13, 1.46)), and current illness (RR 1.52 (1.10, 2.09)). Catch-up growth among IUGR children did not occur. A steady decline in the growth of NBW children resulted in similar anthropometric outcomes by 2 years of age between the two groups.

Birth Weight↗