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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 73 records · Page 4Linked to original sources

The Southwestern Ontario Joint Replacement Pilot Project: electronic point-of-care data collection. Southwestern Ontario Study Group.

OBJECTIVE: To pilot a provincial joint replacement registry using electronic point-of-care data collection. DESIGN: Data collection study. SETTING: Southwestern Ontario, which has a population base of 3.5 million people. PARTICIPANTS: Eighteen orthopedic surgeons. METHOD: Information on total hip and knee replacements was obtained by the orthopedic surgeons over a 6-month period. Information was obtained in paper form and electronically on hand-held computers. MAIN OUTCOME MEASURES: Patient demographics, waiting times from referral to operation, patient satisfaction and relevance and value of electronic records compared with paper records. MAIN RESULTS: Data were collected on 815 total hip and knee arthroplasties. A slightly greater number of hips required revision than knees. The majority of patients were in the 60 to 90-year age range. With respect to the waiting time from referral to operation 10% of patients waited less than 5 weeks, 50% waited less than 30 weeks, and 90% waited less than 59 weeks. There was a high level of patient satisfaction with the operation and with hospital care received. Most surgeons found that the gathering and use of data electronically was relevant and easy. The electronic data were more timely, accurate and complete than paper records. CONCLUSION: Electronic point-of-care data collection is appropriate, particularly in high-volume, high-cost surgical interventions such as total joint replacements.

Adult↗

Improvement in quality of life after bilateral transthoracic endoscopic sympathectomy for palmar hyperhydrosis.

OBJECTIVE: To evaluate the efficacy of bilateral transthoracic endoscopic sympathectomy (TES), in alleviating symptoms and improving quality of life for patients in Hawaii. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients who had undergone TES were evaluated by phone interview and the SF-36 questionnaire to assess improvements in symptoms and the development of compensatory hyperhydrosis. SF-36 scores were divided into 8 scales and evaluated by one-tailed t-test. RESULTS: Since 1999, eight patients (five women and three men, mean age 27.4 years old, range 15-41 yrs) underwent TES without significant complication. Length of hospital stay was less than one day for all patients except one, who stayed four days. Estimated operative blood lost was less than 100 ml and no blood transfusions were required. No Horner's syndrome was suffered. After a mean follow-up of 7.0 months (range 1.2-15.8 months), none of the patients had recurrent symptoms in the palms but all reported moderate compensatory hyperhydrosis located mainly in the trunk and lower extremities (two patients). SF-36 scores showed significant improvements in social functioning (p < 0.005), mental health (p < 0.049), and role-physical (p < 0.020) along with an increase in bodily pain (p < 0.012). CONCLUSION: Although TES resulted in some bodily pain and compensatory hyperhydrosis; these elements were outweighed by the improvement in palmar symptoms, social, mental, and role physical functioning, and overall quality of life.

Adult↗

Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis.

Werner syndrome (WS) is a progeroid syndrome caused by autosomal recessive null mutations at the WRN locus. The WRN gene encodes a nuclear protein of 180 kD that contains both exonuclease and helicase domains. WS patients develop various forms of arteriosclerosis, particularly atherosclerosis, and medial calcinosis. The most common cause of death in Caucasian subjects with WS is myocardial infarction. Previous studies have identified specific polymorphisms within WRN that may modulate the risk of atherosclerosis. Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis. Frequencies of the 1074Leu/Phe polymorphisms in Finnish and Mexican populations revealed an age-dependent decline of 1074Phe/Phe genotype. In Mexican newborns, but not in Finnish newborns, the 1074Leu/Phe and 1367Cys/ Arg polymorphisms were in linkage disequilibrium. Among coronary artery disease subjects, there was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. Furthermore, the 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, as measured by NV50, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance. Samples from Mexican patients with ischemic stroke showed a trend of haplotype frequencies different from that in a control group of Mexican adults. These data support the hypothesis that WRN may mediate not only WS, but may also modulate more common age-related disorders and, perhaps, a basic aging process.

Adult↗

Duplication of chromosome region 4q28.3-qter in monozygotic twins with discordant phenotypes.

We describe monozygotic twins with partially discordant phenotypes who were found to have a duplication of chromosome region 4q28.3-qter. The duplicated region of chromosome 4 resulted from an unbalanced segregation of a balanced maternal (4;22)(q28.3;p13) translocation. Duplication of the long arm of chromosome 4 has been described in >60 patients; however, it usually results from the unbalanced segregation of a parental balanced translocation and has an associated monosomy. Twenty cases of dup 4q without an associated monosomy have been reported, and this is the only case of dup 4q28. 3-qter. All cases of dup 4q are reviewed, and phenotypic aspects are analyzed. Issues of monozygotic twinning and other birth defects also are addressed.

Chromosome Aberrations↗

The prevalence of human herpesvirus-7 in renal transplant recipients is unaffected by oral or intravenous ganciclovir.

The purpose of this study was to compare the prevalence of human herpesvirus (HHV)-7 and cytomegalovirus (CMV) viremia and the effects of oral and intravenous (iv) ganciclovir in renal transplant recipients at risk for CMV. Stored lysates from peripheral blood leukocytes from 92 patients, who had been previously analyzed for CMV viremia by polymerase chain reaction (PCR) for 12 weeks after transplantation, were analyzed for HHV-7 viremia. Baseline and peak prevalences of HHV-7 viremia were 22% and 54%, respectively (P<. 0001). Eighty-two (89%) of 92 patients had at least 1 positive PCR for HHV-7. Oral ganciclovir and treatment with iv ganciclovir had no effect on the prevalence of HHV-7 viremia. In contrast, CMV was almost completely suppressed in patients who received oral ganciclovir, and when present, CMV responded to iv therapy. These results indicate that HHV-7 is resistant to ganciclovir at levels that were effective for prevention and treatment of CMV.

Administration, Oral↗

Diagnostic dilemma

In those issues in which our regular Case of the Month does not appear, The Green Journal will present a Diagnostic Dilemma-an electrocardiogram and/or radiograph with a brief case history-for our readers to solve. The correct answer appears on p. 511 of this issue.If you would like to contribute a Diagnostic Dilemma, please submit a high-quality copy of the EKG or radiograph with a brief synopsis (<250 words) of the case to The American Journal of Medicine's editorial office.

Journal Article↗

Positioning of the mitotic spindle by a cortical-microtubule capture mechanism.

Correct positioning of the mitotic spindle is critical for cell division and development. Spindle positioning involves a search-and-capture mechanism whereby dynamic microtubules find and then interact with specific sites on the submembrane cortex. Genetic, biochemical, and imaging experiments suggest a mechanism for cortical-microtubule capture. Bim1p, located at microtubule distal ends, bound Kar9p, a protein associated with the daughter cell cortex. Bim1p is the yeast ortholog of human EB1, a binding partner for the adenomatous polyposis coli tumor suppressor. EB1 family proteins may have a general role in linking the microtubule cytoskeleton to cortical polarity determinants.

Adenomatous Polyposis Coli Protein↗

Caveolar structure and protein sorting are maintained in NIH 3T3 cells independent of glycosphingolipid depletion.

Glycosphingolipids have been proposed to be critical components of clustered lipids within cell membranes that serve as rafts for the attachment and sorting of proteins to the cell membrane. Density gradient centrifugation was used to isolate and to ascertain the lipid composition of caveolin-enriched membranes. These membranes demonstrated a significant enrichment of sphingolipids and cholesterol containing up to 20 and 30%, respectively, of the cellular glucosylceramide and lactosylceramide. A specific inhibitor of glucosylceramide synthase, d-threo-1-phenyl-2-palmitoyl-3-pyrrolidino-propanol, was used to test the hypothesis that glycosphingolipids are required for the sorting of proteins to caveolae. When NIH 3T3 cells were depleted of their glucosylceramide based glycosphingolipid mass, the caveolar structure remained intact as determined by electron microscopy and confocal microscopy. The caveolar proteins caveolin and annexin II sorted normally to caveolae, as determined by immunoblotting and confocal microscopy. When the GPI-linked protein B61 was inducibly expressed in these cells, sorting to caveolar membranes occurred normally, even in the presence of glucosylceramide depletion. These observations suggest that protein sorting to caveolae in fibroblasts occurs independently of glycosphingolipid synthesis.

3T3 Cells↗

Chromosomal localization, genomic characterization, and mapping to the Noonan syndrome critical region of the human Deltex (DTX1) gene.

The human Deltex (DTX1) gene encodes a cytoplasmic protein that functions as a positive regulator of the Notch signaling pathway. We have determined the genomic organization and map location of the human gene. DTX1 encodes a 2.5-kb cDNA that is composed of nine exons. The DTX1 gene maps to chromosomal region 12q24 in the vicinity of the Noonan syndrome critical region. We have fine-mapped DTX1 to within this critical region and evaluate it as a candidate gene for this disorder.

Carrier Proteins↗

Reactive pulmonary artery vasoconstriction in pulmonary consolidation evaluated by color Doppler ultrasonography.

A total of 122 patients with pulmonary consolidation on chest radiographs underwent color Doppler ultrasonography to evaluate hemodynamic change in regional pulmonary artery in pulmonary consolidation due to various causes. The diseases underlying pulmonary consolidation included 66 simple pneumonia, 37 obstructive pneumonia, 13 tumor consolidation and 6 pulmonary infarctions. Blood flow signals in consolidation were detected by color-flow mapping. The degree of reactive vasoconstriction was evaluated from analysis of the spectral waveform of the blood flow in the segmental pulmonary artery by several vessel resistance-indicating Doppler ultrasound (US) indices, including pulsativity index (PI), resistive index (RI), and acceleration time (AT). The results showed that reactive vasoconstriction was most marked in obstructive pneumonia, followed by simple pneumonia, and least in tumor consolidation (p < 0.001, Kruskal-Wallis test and p < 0.001, Dunn's test for comparison of PI, RI and AT values between different groups of pulmonary consolidation). No flow was detected in pulmonary infarction. We conclude that color Doppler US is a useful tool for evaluating reactive vasoconstriction in pulmonary consolidation. The different degrees of reactive vasoconstriction may be helpful in exploring the possible etiology of pulmonary consolidation.

Blood Flow Velocity↗

Glycosphingolipid depletion in fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase.

BACKGROUND: Fabry disease is an inherited X-linked disorder resulting in the loss of activity of the lysosomal hydrolase alpha-galactosidase A and causing the clinical manifestations of renal failure, cerebral vascular disease, and myocardial infarction. The phenotypic expression of this disorder is manifest by the accumulation of glycosphingolipids containing alpha-galactosyl linkages, most prominently globotriaosylceramide. METHODS: Based on quantitative structure activity studies, we recently reported two newly designed glucosylceramide synthase inhibitors based on 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4). These inhibitors, 4'-hydroxy-P4 and ethylenedioxy-P4, were evaluated for their ability to deplete globotriaosylceramide and other glucosylceramide-based lipids in Fabry lymphocytes and were compared with N-butyldeoxynojirimycin, another reported glucosylceramide synthase inhibitor. RESULTS: Concentrations as low as 10 nmol/L of 4'-hydroxy-P4 and ethylenedioxy-P4 resulted in 70 and 80% depletion, respectively, of globotriaosylceramide, with maximal depletion occurring at three days of treatment. There was no impairment of cell growth. In contrast, N-butyldeoxynojirimycin only minimally lowered globotriaosylceramide levels, even at concentrations as high as 10 micromol/L. Globotriaosylceramide depletion was confirmed by the loss of binding of FITC-conjugated verotoxin B subunit to the lymphoblasts. CONCLUSIONS: These findings suggest that selective glucosylceramide synthase inhibitors are highly effective in the depletion of globotriaosylceramide from Fabry cell lines. We suggest that these compounds have potential therapeutic utility in the treatment of Fabry disease.

1-Deoxynojirimycin↗

Ultrasonographic ear length measurement in normal second- and third-trimester fetuses.

OBJECTIVE: We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. STUDY DESIGN: Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population. RESULTS: A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001). CONCLUSION: The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

Amniocentesis↗

Early cephamycin biosynthetic genes are expressed from a polycistronic transcript in Streptomyces clavuligerus.

A polycistronic transcript that is initiated at the lat promoter has been implicated in the expression of the genes involved in early steps of cephamycin C biosynthesis in Streptomyces clavuligerus. pcbC is also expressed as a monocistronic transcript from its own promoter. However, an alternative interpretation involving expression via three separate yet interdependent transcripts has also been proposed. To distinguish between these possibilities, mutants lacking the lat promoter and containing a transcription terminator within the lat gene (Deltalat::tsr/term mutants) were created. This mutation eliminated the production of lysine-epsilon-aminotransferase (the lat gene product) but also affected the expression of downstream genes, indicating an operon arrangement. Production of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) (the pcbAB gene product) was eliminated in Deltalat::tsr/term mutants, while production of isopenicillin N synthase (IPNS) (the pcbC gene product) was greatly reduced. The provision of alpha-aminoadipate to the Deltalat::tsr/term mutants, either via exogenous feeding or via lat gene complementation, did not restore production of ACVS or IPNS. Analysis of RNA isolated from the Deltalat::tsr/term mutants confirmed that the polycistronic transcript was absent but also indicated that monocistronic pcbC transcript levels were greatly decreased. In contrast, Deltalat mutants created by in-frame internal deletion of lat maintained the polycistronic transcript and allowed production of wild-type levels of both ACVS and IPNS.

Cephamycins↗