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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 433 records · Page 24Linked to original sources

MYB transcription factors in plants.

The cloning of the first transcription factor from plants, the C1 gene of maize, indicated that plants use transcription factors that are structurally related to those of animals in their control of gene expression, because C1 showed significant structural homology to the vertebrate cellular proto-oncogene c-MYB. Since 1987, the catalogue of MYB-related transcription factors has increased considerably in size due, primarily, to the ever-expanding number of MYB genes identified in higher plants (Arabidopsis thaliana is estimated to contain more than a hundred MYB genes). In vertebrates, the MYB-related proto-oncogenes comprise a small family with a central role in controlling cellular proliferation and commitment to development. However, while the functions of some plant MYB genes are relatively well understood they are, at present, quite distinct from their animal counterparts.

Amino Acid Sequence↗

An Escherichia coli CS31A fibrillum chimera capable of inducing memory antibodies in outbred mice following booster immunization with the entero-pathogenic coronavirus transmissible gastroenteritis virus.

CS31A fibrillae are thin, flexible, heteropolymeric proteinaceous appendages exposed as a capsule-like material around the cell surface of certain Escherichia coli strains. Two antigenic peptides of the S spike glycoprotein (TGEV-S) amino acids (aa) 363-371 and 521-531 of the transmissible gastroenteritis virus (TGEV) were tandemly introduced in the loop-structured, variable region aa 202-218 of the major ClpG subunit protein composing the bulk of CS31A. The resulting hybrid fibrillae with a 25 aa heterologous peptide were produced at the cell surface. Using a monoclonal antibody (Mab) specific for the TGEV epitopes, purified hybrid fibrillae were analysed in Western blotting under native conditions, which showed that the two viral epitopes were recognized immunologically as an integral part of the hybrid fibrillae, and therefore that they were antigenically active. The immunogenicity of the fusion construct was evaluated with live recombinant bacteria, purified hybrid ClpG monomers, and purified chimeric CS31A polymers. Whatever the form of hybrid used as antigen, intraperitoneally immunized outbred mice elicited serum anti-TGEV peptides antibodies (Abs) with significant titres and capable of recognizing native TGEV particles, indicating that the epitopes are exposed in an immunogenic conformation in all cases. However, virus neutralization titres were only obtained after immunization with either purified polymers or monomers. Furthermore, 4 months after an ultimate immunization with 20 micrograms of hybrid fibrillae mice developed a strong anamnestic Ab response against the two TGEV peptides following booster inoculation with virions. We conclude that CS31A fibrillae carrying a combination of TGEV epitopes as insert can induce an immunological memory in outbred animals infected with TGEV, and therefore that hybrid CS31A fibrillae may prove efficient as components of a subunit vaccine.

Adhesins, Escherichia coli↗

Diminishing returns or appropriate treatment strategy?--an analysis of short-term outcomes after pain clinic treatment.

In the United Kingdom patients with chronic pain are frequently managed in anaesthetist-led outpatient pain clinics. In many of these clinics the emphasis is on medical therapies (analgesics and psychotropic drugs, TENS, acupuncture and nerve blocks) with patients trying a series of different therapies until relief is achieved or further attempts at physical treatments are discontinued. The sequential trial of different treatment modalities presents clinicians with a problem. Patients who receive little benefit from (say) the first three treatments tried might be expected to be less likely to gain benefit from the next treatment modality. The presence or absence of such 'diminishing returns' from treatment will influence when therapeutic efforts based on the medical model of pain should be abandoned. This study examined basic outcome data on 1912 patients seen in a single Scottish pain clinic between 1987 and 1994. The data were analysed to assess whether the success of treatment modalities depended on whether they were used as a first-choice treatment or were given after previous therapeutic attempts had failed. Diminution in success rates was generally not large although this varied between therapies. No fall-off in success rates was seen for antidepressants, acupuncture or sympathetic nerve blocks. However, the other nerve blocks all showed falling success rates when they were used as fourth- or fifth-line treatments. That little diminution of success rates was seen warrants further investigation. Pain clinics need good information on the success or otherwise of late treatment so that they can devise rational pain management strategies covering multiple therapies and appropriate criteria for ending medical interventions. These findings suggest that allowing patients access to multiple pain therapies may well be an appropriate management strategy.

Adult↗

[Perioperative antibiotic prophylaxis practice of French anesthesiologists and resuscitators: results of a national survey].

Antibiotics are the most prescribed drugs in French hospitals in one third of cases they are used for antiobiotic prophylaxis in surgery. In spite of the guidelines for antibioprophylaxis produced in the last years, their prescription patterns remain still often inappropriate. This survey aimed to assess whether the prescription of antibiotics for prophylaxis by French anaesthetits complied with the French recommendations for antibioprophylaxis in surgery. It focused on the recommended agents, the time of the first injection, the duration of treatment. A sample of 1,473 anaesthetists participated in the survey. In 93% of cases, the first injection of the antibiotic took place at anaesthesia induction, as specified by the recommendations. Cephalosporins of the first and second generation were often administered, as well as the association amoxicillin-clavulanic acid. In contradiction with the recommendations, the cephalosporins of the third generation were widely prescribed in digestive and urological surgery, and the quinolones in urology and ophtalmology. The duration of treatment was restricted to 48 hours by 94% of anaesthetists. However there was a strong tendency to prolonge it in immunodepressed patients and in case of major surgery. This survey showed disparities between the French recommendations for antibioprophylaxis in surgery and the prescription patterns of anaesthetists. The lack of compliance occurred mainly for recent cephalosporins and treatment duration of over 48 hours. It is concluded that a stronger adherence to the principles of antibioprophylaxis is required in surgical patients.

Anesthesiology↗

Study of some phagocyte membrane receptors in patients receiving intravenous polyvalent immunoglobulins as adjunct treatment for nosocomial pneumonia.

PURPOSE: Phagocytosis is a major mechanism of defense against bacterial infections. The ingestion of bacteria by phagocytes involves a variety of cell membrane recognition structures and, among them, immunoglobulin receptors. The aim of this study was to test the phagocytic activity of granulocytes and monocytes of intensive care unit (ICU) patients, and to evaluate the effects of intravenous polyvalent immunoglobulins (IVIG) used as adjunct treatment of nosocomial pneumonia on some phagocyte membrane receptors of these patients. MATERIALS AND METHODS: The phagocytic activity of granulocytes and monocytes of 41 mechanically ventilated patients with nosocomial bacterial pneumonia was studied during the acute phase of infection. These ICU patients were compared with 21 hospitalized, noninfected volunteer patients hospitalized in a medical ward. Peripheral blood granulocytes and monocytes were studied. Of the 41 ICU patients, after randomization, 21 received IVIG at a dose of 1 g/kg for 3 days. The 41 ICU patients were compared with the 21 non-ICU, noninfected hospitalized controls. The 21 ICU patients who received 3 days of IVIG were also compared with the 20 ICU patients not receiving IVIG. Cells were tested in standard immunoglobulin-free medium (fetal calf serum) and in the presence of patients' serum. Blood granulocytes and monocytes were purified and separately exposed to three types of particles: antibody-coated erythrocytes (to test immunoglobulin receptors), opsonized zymosan (to test C3 receptors), and glutaraldehyde-treated erythrocytes (to test lectinlike or other nonspecific binding sites). Phagocytosis and superoxide anion production (oxidative burst) were measured. RESULTS: Granulocytes of ICU patients compared with those of non-ICU, noninfected patients exhibited a substantial decrease of zymosan ingestion (P < .05), whereas phagocytosis of other particles was normal. Monocytes from the ICU patients, compared with those of the non-ICU, noninfected patients, displayed an unselective overall decrease of phagocytic ability for the three particle types (P < .05). The phagocytosis activity of the three membrane receptor species of blood monocytes and granulocytes of ICU patients was not significantly modified by the IVIG infusion. For both monocytes and granulocytes, no significant improvement was observed in the fraction of cells that ingested at least one foreign particle and the mean number of particles per cell having phagocytized at least one foreign particle. Granulocyte and monocyte functions were also tested by the production of reduced ferricytochrome and no significant improvement in the oxidative burst was observed after infusion of IVIG. CONCLUSION: Infected ICU patients display a deficiency of phagocytosis membrane receptors of blood granulocytes and monocytes. The addition of IVIG to standard therapy does not improve the phagocytic activity of ICU patients with nosocomial pneumonia.

Adult↗

Human uropathogenic and bovine septicaemic Escherichia coli strains carry an identical F17-related adhesin.

Pathogenic Escherichia coli produce fimbriae which mediate binding to mucosal cells. Generally, different fimbriae are associated with different tissular tropisms and different host specificities. Genes encoding for pilin and adhesin subunits of two F17-related fimbriae were cloned and sequenced. The first, G fimbriae, are synthesized by a human uropathogenic E. coli strain, and the second, 20K fimbriae, by a bovine septicaemic E. coli strain. We showed that both fimbriae are identical and present a high homology with F17a and F17b fimbriae synthesized by bovine enterotoxigenic E. coli strains. Furthermore, data showed that the G adhesin did not mediate adhesion to human uroepithelial cells, suggesting that it is not responsible for the urinary tropism of the strain and confirming the intestinal tropism specificity of F17-related adhesins.

Adhesins, Escherichia coli↗

Preventive effects of two PAF-antagonists, PMS 536 and PMS 549, on cyclosporin-induced LLC-PK1 oxidative injury.

The present study was undertaken to evaluate the effects of platelet activating factor (PAF) antagonists, PMS 536 and PMS 549, on LLC-PK1 toxicity induced by Cyclosporin A (CsA). The LLC-PK1 cell line was used as an in vitro model. CsA cytotoxicity was determined in relation with ATP content. Alkaline phosphatase and N-acetyl-beta-glucosaminidase activities, which are directly correlated with tubular cell damage, were used as markers for renal injury. CsA alone provoked in the LLC-PK1 cell line a marked decrease in cell viability (55%) and membrane integrity (56%), and a significant increase in AP and NAG activities and in oxidized glutathione level. The ATP decrease and the ADP increase, resulting in a decline of the ATP/ADP ratio, is indicative of an anoxic energy charge. Co-treatment with CsA plus PMS 536 or PMS 549 resulted in a minor decrease in cell viability and in significant membrane integrity recovery. Moreover, the ATP depletion and the increase in ATP metabolites, hypoxanthine and uric acid induced by CsA were strongly prevented by PAF antagonists. In contrast, GSSG level remained high as in CsA-treated cells, but GSH level was in the range of controls. Our results suggest that both PAF antagonists attenuate CsA oxidative injury and prevent energy metabolism disturbances probably by maintaining cell integrity. The lipophilicity of both molecules may be responsible for membrane stabilization and may confer the protective effects observed in energy metabolism. The results obtained with PMS 536 and PMS 549 are indicative of interactions between PAF and CsA in renal injury and suggest the therapeutic potential of these PAF-antagonists against CsA-induced nephrotoxicity.

Acetylglucosaminidase↗

The multi-drug resistance reversal agent SR33557 and modulation of vinca alkaloid binding to P-glycoprotein by an allosteric interaction.

1. The interaction of the indolizin sulfone SR33557 with the multidrug resistance P-glycoprotein (P-gp), was used to explore the nature of drug binding site(s) on this transporter. The steady-state accumulation of [3H]-vinblastine in P-gp expressing CHrB30 cells was increased by SR33557 with greater potency than verapamil. Furthermore, SR33557 potentiated the affinity of verapamil to modulate vinblastine transport when added simultaneously. 2. Verapamil elicited a 1.5 to 2.5 fold stimulation of basal ATPase activity in CHrB30 membranes, whereas SR33557 and vinblastine inhibited activity, but only at relatively high concentrations. However, SR33557 and vinblastine decreased the Vmax but not the Km for verapamil stimulation of ATPase activity. This is indicative of a non-competitive interaction, most likely at distinct sites. 3. The specific [3H]-vinblastine binding to P-gp in CHrB30 cell membranes was displaced by SR33557 with an IC50 of 8.3 +/- 4.5 nM. Moreover, SR33557 caused a 3 fold increase in the dissociation rate of vinblastine binding to P-gp indicating a negative allosteric effect on the vinca alkaloid acceptor site. 4. These results demonstrate that SR33557 interacts with a site on P-gp which is distinct from, but allosterically linked to the vinca alkaloid site. The apparent broad substrate specificity displayed by P-gp may be explained by a multiple drug binding site model.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Tam3 produces a suppressible allele of the DAG locus of Antirrhinum majus similar to Mu-suppressible alleles of maize.

Tam3 from Antirrhinum majus belongs to the Ac/Ds family of transposable elements. An allele of the DAG locus of Antirrhinum (dag::Tam3), which is required for chloroplast development and leaf palisade differentiation, has been generated by Tam3 insertion into the untranslated leader sequence of the gene. This allele gives rise to a cold-sensitive phenotype, where mutant tissue containing wild-type revertant somatic sections is observed in the leaves of plants grown at 15 degrees C, while leaves of plants grown at 25 degrees C appear near wild-type. The temperature sensitivity of dag::Tam3 results from expression of the DAG locus responding to the activity of the transposable element, the transposition of which is very sensitive to growing temperature. Genetic suppression of Tam3 transposition, using the STABILISER locus, also results in suppression of the dag mutant phenotype. dag::Tam3 represents a Tam3-suppressible allele similar to those described for Mu transposons in maize. Suppression of the dag mutant phenotype in response to element inactivation appears to result from use of an alternative promoter at the 3' end of the Tam3 element. The production of suppressible alleles by an Ac-like element is discussed in relation to the mutagenic potential of plant transposons in producing complex genetic diversity.

Alleles↗

Concentrations of prophylactic ceftriaxone in abdominal tissues during pancreatic surgery.

Ceftriaxone concentrations in abdominal tissues were evaluated after administration as antibiotic prophylaxis for pancreatic surgery. Ten patients were given ceftriaxone (1 g i.v.) 30 min before surgery. Ceftriaxone concentrations in fatty tissues ranged from 2.5 to 6.2 microg/g. Ceftriaxone concentrations were 6.0 +/- 8.6 microg/g in pancreatic tissues, 2.1 +/- 2.5 mg/L in pancreatic fluid, 1179 +/- 1271 mg/L in pancreatic bile, and 18 +/- 16 microg/g in the liver. In fatty tissues, 8-10 patients had tissue levels greater than the MIC90 for Staphylococcus aureus and Escherichia coli and the 10 patients had tissue levels greater than the MIC90 for Klebsiella pneumoniae and Proteus mirabilis. In other tissues, penetration was greater than the MIC90 for potential pathogens in 50-100% of the patients.

Abdominal Muscles↗

Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation.

BACKGROUND: The potential adverse effects of ketamine in neurosurgical anesthesia have been well established and involve increased intracranial pressure (ICP) and cerebral blood flow. However, reexamination of ketamine is warranted because data regarding the effects of ketamine on cerebral hemodynamics are conflicting. METHODS: Eight patients with traumatic brain injury were studied. In all patients, ICP monitoring was instituted before the study. Control of ICP (less than 25 mmHg), hemodynamic values, and blood gas tension (partial pressure of carbon dioxide in arterial blood between 35-38 mmHg) was obtained with propofol infusion (3 mg x kg(-1) x h(-1)) and mechanical ventilation. The effects of three doses of ketamine, 1.5, 3, and 5 mg/kg, respectively, on ICP, cerebral perfusion pressure, jugular vein bulb oxygen saturation, middle cerebral artery blood flow velocity, and electric activity of the brain (EEG) were measured. The three doses were administered intravenously at 6-h intervals over 30 s through a central venous line. Systemic and cerebral hemodynamics and end-tidal carbon dioxide were continuously monitored and recorded at 1-min intervals throughout the 30-min study periods. RESULTS: Ketamine, in all three doses studied (1.5, 3, and 5 mg/kg) was associated with a significant decrease in ICP (mean +/- SD: 2 +/- 0.5 mmHg [P < 0.05], 4 +/- 1 mmHg [P < 0.05], and 5 +/- 2 mmHg [P < 0.05]) among the study patients regardless of the ketamine dose used. There were no significant differences in cerebral perfusion pressure, jugular vein bulb oxygen saturation, and middle cerebral artery blood flow velocity. Ketamine induced a low-amplitude fast-activity electroencephalogram, with marked depression, such as burst suppression. CONCLUSIONS: These results suggest that ketamine may not adversely alter cerebral hemodynamics of mechanically ventilated head-trauma patients sedated with propofol. These encouraging results should be confirmed in larger groups of similar patients.

Adolescent↗

Safety profile of gemcitabine, a novel anticancer agent, in non-small cell lung cancer.

Gemcitabine is a novel anticancer agent showing activity with relatively mild toxicity across a range of solid tumors including non-small cell lung cancer (NSCLC). In studies using similar doses and schedules, consistent response rates of around 20% were recorded in NSCLC. In an integrated safety study using data from 360 patients with NSCLC, gemcitabine exhibits a mild safety profile for such an active drug. Hematological toxicity is mild and short lasting, and the level of infection associated with this degree of myelosuppression was low. Mild transaminase elevations occurred frequently but were not progressive or dose limiting. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose limiting and generally well controlled with standard antiemetics. Mild flu-like symptoms were experienced in a small proportion of patients and rarely resulted in discontinuation. Where edema or peripheral edema were experienced, there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare and there was no grade 4 alopecia. In conclusion, gemcitabine is a promising new agent in the treatment of NSCLC. Its mild toxicity which is non-overlapping with other cytotoxics has prompted investigation into its use in combination with other chemotherapy regimens.

Adolescent↗

Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma.

OBJECTIVE: To compare the patterns of evolution of two proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6 [IL-6]) in two major clinical entities associated with systemic inflammatory response: septic shock and multiple trauma (with and without hemorrhagic shock). DESIGN: Prospective study of two cohorts of patients. SETTING: Critical care unit and Emergency Center of a university hospital. PATIENTS: Twenty-five nontrauma patients with septic shock and 60 multiple trauma patients (of whom eight patients were resuscitated from hemorrhagic shock). INTERVENTIONS: Serial blood samples were collected in each patient for determination of serum cytokine concentrations. Samples were obtained over 7 days in septic shock patients and 11 days in trauma patients. Standard resuscitation techniques were used in each patient. Clinical and laboratory data were prospectively collected. MEASUREMENTS AND MAIN RESULTS: High concentrations of circulating TNF-alpha and IL-6 were found in patients with septic shock. High IL-6 concentrations, but normal TNF-alpha concentrations were detected in trauma patients. At study entry, TNF-alpha concentrations were higher in nonsurvivor septic shock than in nonsurvivor trauma patients (42 +/- 7 vs 13 +/- 2 pg/mL; p < .001). During the whole study period, nonsurvivor septic shock patients maintained higher TNF-alpha concentrations than nonsurvivor trauma patients (p < .001). In survivors in both groups, normal values for TNF-alpha were detected during the whole study period. At study entry, IL-6 concentrations were significantly higher in nonsurvivor septic shock patients than in nonsurvivor trauma patients (15,627 +/- 4336 vs. 317 +/- 124 pg/mL; p < .0001). During the whole study period, much higher concentrations of IL-6 were detected in septic shock patients than in trauma patients (p < .0001). In survivors, at study entry, IL-6 concentrations were much higher in septic shock patients than in trauma patients (3947 +/- 1410 vs. 247 +/- 41 pg/mL; p < .001). Higher IL-6 concentrations were maintained throughout the study period in septic shock patients than in trauma patients (p < .001). In septic shock patients, changes in both TNF-alpha and IL-6 were correlated with outcome, higher values being found in patients likely to die. Neither TNF-alpha nor IL-6 values were of any significant value in predicting outcome of trauma patients. When septic shock patients were compared with traumatized patients resuscitated from hemorrhagic shock, the former had much higher concentrations of both TNF-alpha and IL-6 throughout the study period (p < .01 to p < .00001). Increased IL-6 values were an indicator of the development of a nosocomial infection in trauma patients. In five trauma patients who developed a nosocomial pneumonia during the study period, the IL-6 concentration was 433 +/- 385 pg/mL before the onset of pneumonia, then peaked at 3970 +/- 1478 pg/mL on day 7, and returned to baseline (219 +/- 58 pg/mL) on day 11. CONCLUSIONS: In septic shock patients, high amounts of circulating TNF-alpha and IL-6 are found and then correlate with fatal outcome. In trauma patients (even those patients resuscitated from hemorrhagic shock), much less increased concentrations of IL-6 are detected while normal TNF-alpha circulating concentrations are measured. In these patients, cytokine concentrations do not correlate with outcome. This finding suggests a much higher degree of activation of the immunoinflammatory cascade in septic shock than in multiple trauma patients. Increased IL-6 values are an indicator of the development of a nosocomial infection in trauma patients.

Adult↗

Lower extremity deep vein thrombosis: a prospective, randomized, controlled trial in comatose or sedated patients undergoing femoral vein catheterization.

OBJECTIVES: To determine the rate of lower extremity deep vein thrombosis after the use of femoral catheters in intensive care unit (ICU) comatose or sedated adults. Results were then compared with results of patients undergoing superior vena cava catheterization. DESIGN: Prospective, randomized, controlled, unblinded study. SETTING: A mixed medical/surgical ICU in a university hospital. PATIENTS: Sixty-one comatose or sedated patients admitted to the ICU who underwent central venous catheterization. INTERVENTIONS: Patients were monitored for signs of thrombotic complications. On catheter removal, a lower-extremity bilateral phlebographic examination was performed in each patient. MEASUREMENTS AND MAIN RESULTS: After randomization, 31 patients underwent femoral vein catheterization and 30 patients underwent superior vena cava catheterization, either by axillary (21 patients) or internal jugular vein (10 patients) cannulation. Single lumen polyurethane catheters were inserted for a mean duration of 7.1 +/- 4.6 (SD) days in the femoral vein group and 9.9 +/- 5.5 days in the superior vena cava group (p = NS). No patient had clinical signs of leg venous thrombosis or pulmonary embolism during the study period. In each patient, lower extremity bilateral phlebography was performed at the time of catheter removal. Leg phlebographies were normal in 18 (60%) patients in the femoral vein group and 26 (84%) patients in the superior vena cava group. Fibrin sleeves which developed around the femoral catheters were seen in seven (23.3%) patients in the femoral vein group and in no patients in the superior vena cava cannulation group. Three patients had femoral vein thrombosis, two (6.6%) patients in the femoral vein group (two nonobstructive thromboses, adherent to the common femoral vein wall) and one (3.0%) patient in the superior vena cava group (nonobstructive thrombosis which developed in the superficial femoral vein) (p = NS). Lower deep extremities thrombosis developed in five (16.7%) patients in the femoral vein group and in five (16%) patients in the superior vena cava group (p = NS). CONCLUSIONS: Femoral vein catheterization with a polyurethane catheter is associated with a lower rate of extremity deep vein thrombosis which is similar to the rate observed after superior vena cannulation in comatose or sedated patients. Femoral vein thrombosis was observed at a rate of 6.6% after femoral vein cannulation and a rate of 3% after superior vena cava cannulation. Given the acceptable rate of this clinically important complication, femoral vein cannulation offers an attractive alternative to insertion via the vena cava in the critically ill.

APACHE↗

A prospective evaluation of the use of femoral venous catheters in critically ill adults.

OBJECTIVE: To determine the rate of complications following the use of femoral catheters in adults. DESIGN: Prospective survey of major and minor complications. SETTING: A mixed medical/surgical intensive care unit (ICU) in a university hospital. PATIENTS: Eighty consecutive patients admitted to the ICU who underwent right femoral venous catheterization over a 13-month period. INTERVENTIONS: Patients were carefully monitored for mechanical, infectious, and thrombotic complications. On catheter removal, a lower extremity bilateral phlebographic examination was performed in each patient. MEASUREMENTS AND MAIN RESULTS: There were 80 polyurethrane catheters inserted for a mean duration of 8.8 +/- 4.4 (SD) days. Catheters were inserted by interns or residents (75%) or by critical care fellows (25%). Minor complications consisted of arterial puncture (15%), local hematoma (4.4%), local bleeding (3%), and local inflammation (5%). After insertion, 17% of catheter tips were in the right atrium, 13% in the abdominal vena cava, 63% in the thoracic inferior vena cava (correct position), and 8% in aberrant abdominal intravascular positions. After repositioning, 80% of catheter tips were in the thoracic inferior vena cava. One patient developed a catheter-related bacteremia. Catheter-related sepsis were seen in three (3.7%) patients and catheter colonization in 11 (13.7%) patients. No patient had clinical signs of deep vein thrombosis or pulmonary embolism. Bilateral phlebography was performed in 70 patients at the time of catheter removal and was normal in 45 (64%) patients. Fibrin sleeves were seen in 11 (15.7%) patients. Lower extremity deep vein thrombosis developed in 24 (34%) patients. Six (8.5%) patients had femoral vein thrombosis (common femoral vein in two patients, and superficial femoral vein in four patients). Eighteen (25.7%) patients developed popliteal vein or posterior tibial vein thrombosis that was either bilateral (n = 16) or homolateral (n = 2) to the femoral catheter. CONCLUSIONS: Based on the data from this study, we conclude that femoral vein catheterization with a polyurethane catheter is associated with an 8.5% frequency rate of femoral vein thrombosis. Thrombosis in the popliteal vein or posterior tibial vein is higher (25.7%), but is homolateral to the catheter with only a 2.8% frequency rate. Infectious complications are low and similar to those of other central venous routes. Given the acceptable rate of clinically important complications, femoral venous catheterization offers an attractive alternate site of insertion to the jugular and subclavian veins for central venous access in the critically ill.

Adult↗

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

Alleles↗