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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 37 records · Page 2Linked to original sources

A pilot study of the continuous glucose monitoring system: clinical decisions and glycemic control after its use in pediatric type 1 diabetic subjects.

OBJECTIVE: To determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) could be used to make clinical decisions and whether it has an impact on glycemia in pediatric type 1 diabetic subjects. RESEARCH DESIGN AND METHODS: Pediatric subjects were recruited if they had HbA(1c) >8.0% with management problems (n = 35) or episodes of severe or nocturnal hypoglycemia or hypoglycemia unawareness associated with HbA(1c) < or =8.0% (n = 12). A total of 47 patients with a mean HbA(1c) value of 8.6 +/- 1.6% (mean age 11.8 +/- 4.6 years, youngest 2.7 years, and diabetes duration 5.5 +/- 3.5 years) on three to four insulin injections/day (n = 24) or insulin pump therapy (n = 23) were followed with the CGMS for a mean of 69.5 +/- 28 h. Comparisons were made between the number of high (>150 mg/dl) and low (<70 mg/dl) glucose patterns discerned with the sensor or the logbook, and HbA(1c) levels were evaluated. RESULTS: In patients on injection therapy, 30 high or low glucose patterns were discerned with the logbook records and 120 patterns with the CGMS. Specific alterations of the diabetes regimen were made. An overall significant change in HbA(1c), from 3 months before wearing the sensor to 6 months after (analysis of variance 0.04), was found in the subjects. Post hoc analysis showed a significant change in HbA(1c) from 8.6 +/- 1.5% at baseline to 8.4 +/- 1.3% at 3 months (paired Student's t test 0.03). CONCLUSIONS: The CGMS can be used by pediatric patients to detect abnormal patterns of glycemia. The information that was obtained could be used to alter the diabetes regimen and impact glycemic outcome.

Adolescent↗

Identification and genomic cloning of CMHC1. A unique myosin heavy chain expressed exclusively in the developing chicken heart.

We report the identification and cloning of a unique chick myosin heavy chain (CMHC1) that is expressed exclusively in the heart during embryogenesis. Using primers specific to myosin heavy chains, we used reverse transcriptase-polymerase chain reaction to clone and isolate CMHC1 from embryonic day 10 chicken heart RNA. Sequence analysis indicated that CMHC1 was a novel member of the myosin heavy chain family. Expression of the CMHC1 transcripts was detected in Hamburger Hamilton stage 10 chick embryos in the fusing myocardium. Expression of CMHC1 was maintained at high levels throughout the tubular heart of later stage embryos. Reverse transcriptase-polymerase chain reaction and in situ hybridizations failed to detect CMHC1 transcripts in the developing somites, limb buds, or skeletal musculature at any stage of chick development. Genomic CMHC1 clones have been isolated that contain sequences approximately 5.2 kilobase upstream of the presumptive CMHC1 transcription start site. Portions of the upstream regulatory region induced a 21-fold increase in reporter gene expression in primary cardiomyocytes. Because of its unique cardiac-restricted expression, CMHC1 will provide an excellent model system to study the molecular mechanisms required for the early developmental regulation of heart-specific genes.

3T3 Cells↗

Phenanthrenequinone antiretroviral agents.

Compounds 3 and 5 are the first phenanthrenequinones to exhibit significant virucidal activity against the retrovirus equine infectious anemia virus. They differ from hypericin in that their virucidal activity is not light dependent.

Animals↗

Antigenic and genetic stability of bovine immunodeficiency virus during long-term persistence in cattle experimentally infected with the BIV(R29) isolate.

Experimental infection of cattle with bovine immunodeficiency virus (BIV) is characterized by persistent, low levels of virus replication in the absence of clinical disease. A virus neutralization (VN) assay was developed to examine the role of VN antibodies in controlling virus replication in cattle experimentally infected with the BIV(R29) isolate of BIV. All animals developed VN antibody, but there was no correlation between VN titres and restriction of virus replication in vivo. BIV infection did not induce high-titred, cross-neutralizing antibody and there was no evidence for antigenic variation through more than 4 years in vivo. Genetic comparisons among the BIV(R29) inoculum virus and viruses isolated from infected animals identified only limited genetic variation during 4 years in vivo. Moreover, there was no evidence that the observed variation was due to selection. Analyses of genetic diversity in the virus stock used for inoculation indicated a fairly homogeneous population. In the absence of high levels of virus replication and overt clinical disease, there appeared to be little selection of virus variants, resulting in antigenic and genetic stability of BIV(R29) during long-term, persistent infection.

Amino Acid Sequence↗

Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas.

UNLABELLED: Preoperative localization of pancreatic neuroendocrine tumors with traditional imaging fails in 40-60% of patients. Endoscopic ultrasound (EUS) is highly sensitive in the detection of these tumors. Previous reports included relatively few patients or required the collaboration of multiple centers. We report the results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors. METHODS: We prospectively used EUS early in the diagnostic evaluation of patients with biochemical or clinical evidence of neuroendocrine tumors. Patients had surgical confirmation of tumor localization or clinical follow-up of >1 yr. RESULTS: Eighty-two patients underwent 91 examinations (cases). Thirty patients had multiple endocrine neoplasia syndrome type 1. One hundred pancreatic tumors were visualized by EUS in 54 different patients. The remaining 28 patients had no pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the tumors were < or =2.0 cm in diameter. Of the 54 explorations with surgical confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50 patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The most common site for tumor localization was the pancreatic head (46 patients). Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was more accurate than angiography with or without stimulation testing (secretin for gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those patients undergoing further imaging procedures. EUS was not reliable in localizing extrapancreatic tumors. CONCLUSIONS: In this series, the largest single center experience reported to date, EUS had an overall sensitivity and accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use of EUS as a primary diagnostic modality in the evaluation and management of patients with neuroendocrine tumors of the pancreas.

Adenoma, Islet Cell↗

Binding of equine infectious anemia virus rev to an exon splicing enhancer mediates alternative splicing and nuclear export of viral mRNAs.

In addition to facilitating the nuclear export of incompletely spliced viral mRNAs, equine infectious anemia virus (EIAV) Rev regulates alternative splicing of the third exon of the tat/rev mRNA. In the presence of Rev, this exon of the bicistronic RNA is skipped in a fraction of the spliced mRNAs. In this report, the cis-acting requirements for exon 3 usage were correlated with sequences necessary for Rev binding and transport of incompletely spliced RNA. The presence of a purine-rich exon splicing enhancer (ESE) was required for exon 3 recognition, and the addition of Rev inhibited exon 3 splicing. Glutathione-S-transferase (GST)-Rev bound to probes containing the ESE, and mutation of GAA repeats to GCA within the ESE inhibited both exon 3 recognition in RNA splicing experiments and GST-Rev binding in vitro. These results suggest that Rev regulates alternative splicing by binding at or near the ESE to block SR protein-ESE interactions. A 57-nucleotide sequence containing the ESE was sufficient to mediate Rev-dependent nuclear export of incompletely spliced RNAs. Rev export activity was significantly inhibited by mutation of the ESE or by trans-complementation with SF2/ASF. These results indicate that the ESE functions as a Rev-responsive element and demonstrate that EIAV Rev mediates exon 3 exclusion through protein-RNA interactions required for efficient export of incompletely spliced viral RNAs.

Alternative Splicing↗

Image-guided sinus surgery: navigation without road maps.

Many otorhinolaryngologists have recognized the necessity of developing new methods to increase the safety of endoscopic sinus surgery and improve patient outcomes. Despite the rapid advances made in the field, serious iatrogenic complications still occur. To counteract these complications, one recent advancement has been the development of a computed tomographic image-guided surgery (IGS) system, which can enhance the ability to treat the crippling effects of sinus disease. These systems have gained a degree of accuracy, making them suitable for difficult surgical procedures, and they may soon become standard of care. The perioperative nurse must understand and be able to work with IGS.

Humans↗

Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy.

In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24.

Chromosomes, Human, Pair 6↗

Cost effectiveness of EUS for preoperative localization of pancreatic endocrine tumors.

BACKGROUND: Endoscopic ultrasonography (EUS) is highly accurate in the localization of small pancreatic tumors. We determined the cost effectiveness of EUS used early in the preoperative evaluation of pancreatic endocrine tumors. METHODS: In a study with a case-control design, 36 patients (19 men, 17 women) who underwent preoperative EUS were matched retrospectively with 36 patients who underwent surgical exploration immediately before the introduction of EUS. The number, cost, and effectiveness of preoperative localization studies, days of hospitalization, and surgical and anesthesia times were assessed. RESULTS: The EUS group had reduced charges for preoperative localization studies: $2620 versus $4846 per patient (p < 0.05), largely because of reductions in the number of diagnostic angiograms and venous sampling procedures performed. Surgical and total anesthesia times were decreased, as were the number of preoperative admissions for angiographic procedures. The cost-effectiveness ratio for the EUS group was $3144 per tumor localized compared with $5628 per tumor localized for the group treated before EUS became available (p < 0.05). CONCLUSION: EUS is highly accurate in the localization of pancreatic neuroendocrine tumors and is cost effective when used early in the preoperative localization strategy. EUS decreased the need for additional invasive tests and avoided unnecessary morbidity and resource consumption. EUS should play a primary role in preoperative localization of pancreatic neuroendocrine tumors.

Angiography↗

Characterization of primary cell cultures as potential target cells for analysis of bovine cytotoxic T lymphocytes.

In domestic animal species, assessment of cell-mediated immune responses to virus infection is hampered by the requirement for class I MHC compatibility between target and effector cells. Additional complicating factors can include an inability to infect target cells in vitro, or virus-induced lysis of infected target cells. One way to circumvent these problems is to use virus-mediated gene transfer to deliver individual viral genes to autologous primary target cells. Several primary bovine cell cultures were assessed as potential target cells for cytotoxic T lymphocyte (CTL) assays by measuring their levels of class I MHC expression and susceptibilities to retroviral gene delivery. High levels in both class I MHC expression and susceptibility to gene delivery were seen in adherent cell cultures isolated from peripheral blood (PBAC). PBAC, which arose as an outgrowth of adherent peripheral blood mononuclear cell cultures, had morphology, protein expression patterns, and response to functional assays characteristic of high endothelial cells. Expression of viral vector-delivered genes in PBAC cells was confirmed with a recombinant retrovirus carrying the green fluorescent protein (GFP) gene. The use of vector-mediated delivery of viral genes to bovine high endothelial cells is a promising method for assessment of cell-mediated immunity in cattle.

Animals↗

Myopathy with trabecular muscle fibers.

A systematic review of muscle biopsies over a 15 year period in a large neurological hospital revealed 21 cases (7% of the total of non-inflammatory myopathies) with a distinctive pattern of myopathology and a limb-girdle clinical phenotype. The muscle pathology was dominated by a large prevalence (20-90%) of trabecular or lobulated fibers in which maldistribution of intermyofibrillar mitochondria produced a lobulated pattern of oxidative enzyme activity on transverse sections. The clinical picture was characterized by adult onset, slowly progressive muscle weakness affecting mainly proximal limb musculature, although mild distal weakness was also present in 60% of the cases. The trabecular pattern of oxidative enzyme reaction reflects maldistribution of the intermyofibrillar mitochondria; this may be caused by malfunction of a putative anchoring mechanism. While trabecular fibers can occur as a nonspecific alteration of muscle fibers in many diverse myopathies, the high prevalence of trabecular fibers as the dominant pathology in trabecular fiber myopathy makes it a distinctive (though not necessarily etiologically homogeneous) clinico-pathological entity.

Adolescent↗

The 13C-urea blood test accurately detects active Helicobacter pylori infection: a United States, multicenter trial.

OBJECTIVES: Current nonendoscopic tests for Helicobacter pylori include antibody tests and the urea breath test. After the administration of 13C-urea, serum bicarbonate measurement can identify those infected with H. pylori. In this study, our aims were to determine the accuracy of the urea blood test, and to compare the accuracy of the urea blood test with that of rapid urease testing of gastric biopsies. METHODS: This was a multicenter trial conducted at five sites within the U.S. Patients scheduled for endoscopy were recruited. During endoscopy, biopsies were obtained from the gastric body and antrum for histology and rapid urease testing. Patients underwent the urea blood test, which required the ingestion of 125 mg of 13C-urea after endoscopy. Thirty minutes later, a 3-ml blood sample was obtained and later analyzed by mass spectrometry for 13C-bicarbonate. Performance characteristics for the urea blood test were calculated using the endoscopic biopsy tests as a gold standard. RESULTS: One hundred and twenty-one patients (54 infected) were enrolled. The urea blood test yielded sensitivity of 89%, specificity of 96%, positive predictive value of 94%, negative predictive value of 91%, and accuracy of 93% using histology as a gold standard. There was no difference between results obtained with the urea blood test and rapid urease testing of gastric biopsies. CONCLUSIONS: The urea blood test accurately identified active H. pylori infection. The performance characteristics of this nonendoscopic test were similar to those of endoscopic rapid urease testing.

Adult↗

Association between diabetes control and visits to a multidisciplinary pediatric diabetes clinic.

OBJECTIVE: To determine if there is a relationship between diabetes outcome as measured by HbA1C and the number of multidisciplinary clinic visits per year in children and youth with diabetes. RESEARCH DESIGN AND METHODS: The number of clinic visits per year, the mean HbA1C (by DCA 2000, Miles, Tarrytown, NY), type of insurance, parental marital status, parental age, maximal parental grade level achieved, family income, self-identified race, and scores on adherence and knowledge tests were compared for 1995 in 360 patients with a mean age of 11.6 +/- 4.8 years (1-2 visits, 85 patients; 3-4 visits, 275 patients), for 1996 in 412 patients with a mean age of 11.6 +/- 4.7 years (1-2 visits, 115 patients; 3-4 visits, 297 patients), and for 1997 in 442 patients with a mean age of 11.8 +/- 4.9 years (1-2 visits, 126 patients; 3-4 visits, 332 patients). RESULTS: There was a significant difference in the mean HbA1C levels between subjects with 1 to 2 visits versus 3 to 4 visits during the 3 years of this study. In 1995, the mean HbA1C was 9.0 +/- 2.0% for subjects with 1 to 2 visits and 8.3 +/- 1.6% for subjects with 3 to 4 visits. In 1996, the mean HbA1C was 9.3 +/- 2.0% for subjects with 1 to 2 visits and 8.4 +/- 1.6% in those with 3 to 4 visits, whereas in 1997, the mean HbA1C was 9.1 +/- 1.9% with 1 to 2 visits and 8.3 +/- 1.5% with 3 to 4 visits. There was a significant difference in the number of visits by the age of the subject. The mean age of patients with 1 to 2 visits was 13.6 +/- 4.5 years; it was 10.8 +/- 4.6 years with 3 to 4 visits. However, for age groups <13 years versus >/=13 years, there was still a difference between HbA1C levels for subjects with 1 to 2 visits compared with 3 to 4 visits (8.9 +/- 1.7% versus 8.1 +/- 1.3%, respectively). The only patient/family characteristic that had an association with number of visits was the marital status of the parents. Children from single-parent households had fewer visits. There was no association between health insurance status and number of visits and there was no difference between the number of visits and the mean scores on tests of adherence or knowledge. Multivariate analysis showed that the number of visits was a significant predictor of HbA1C even after controlling for age, duration of diabetes, and scores on adherence and knowledge tests. CONCLUSIONS: The finding that subjects with more frequent visits to a multidisciplinary diabetes clinic had lower HbA1C levels during the 3 years of this study suggests that strategies should be developed to promote adherence with quarterly visits, particularly targeted to children from single-parent households and to teens.

Adolescent↗

Use of a plastic insulin dosage guide to correct blood glucose levels out of the target range and for carbohydrate counting in subjects with type 1 diabetes.

OBJECTIVE: To improve glycemic control, a hand-held plastic Insulin Dosage Guide was developed to correct blood glucose levels outside of the target range. RESEARCH DESIGN AND METHODS: Protocol 1: Some 40 children (mean age 10.6+/-4.6 years) were randomly assigned for 3 months to use a written-on-paper algorithm or the Insulin Dosage Guide to correct abnormal blood glucose levels. Mean HbA1c and blood glucose levels and time to teach insulin dosage correction were compared. Protocol 2: The Insulin Dosage Guide was used by 83 subjects (mean age 11.4+/-4.3 years) for 1 year, and mean HbA1c levels, blood glucose levels, and number of consecutive high blood glucose values taken before and after the year were compared. Protocol 3: Some 20 patients (mean age 10.1+/-3.7 years) using rapid-acting insulin and 64 patients (mean age 15.9+/-3.6 years) using an insulin pump and rapid-acting insulin used the Insulin Dosage Guide and had mean blood glucose levels, HbA1c, and percentage of blood glucose levels outside of the target range determined. RESULTS: Protocol 1: There was a significant reduction in mean HbA1c (P = 0.04) and blood glucose levels (P = 0.05) and in the time needed to teach how to correct blood glucose values using the Insulin Dosage Guide compared with the paper algorithm. Protocol 2: There was a decrease in mean HbA1c levels (P = 0.0001) and a decrease in the mean number of consecutive blood glucose levels (P = 0.001) over the 1-year time period. Protocol 3: With rapid-acting insulin, there was a significant increase in the percentage of blood glucose levels within the target range (1 month, P = 0.04; at 3 months, P = 0.03). With the insulin pump, there was a high rate (90%) of blood glucose levels in the target range during pump initiation when the Insulin Dosage Guide was used. CONCLUSIONS: This inexpensive hand-held plastic card, which is portable and easy to use, may help patients improve glycemia and successfully manage diabetes.

Adolescent↗