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Biomedical subjects

E Sande

Publications and source records attributed to E Sande.

14 recordsLinked to original sources

Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48.

A site-specific C to U editing reaction modifies nuclear apolipoprotein B100 (apoB100) mRNA, producing apolipoprotein B48 in the mammalian small intestine. This reaction is mediated by a multicomponent enzyme complex, which contains a catalytic subunit, Apobec-1. We have used gene targeting to disrupt mouse apobec-1 in order to establish its requisite importance in apoB mRNA editing and also, in view of its widespread tissue distribution in rodents, as a preliminary indication of other potential roles. Both heterozygous (apobec-1+/-) and homozygous (apobec-1-/-) gene-targeted mice appear healthy and fertile with no alterations in serum cholesterol or triglyceride concentrations. The apobec-1+/- mice demonstrated reduced levels of hepatic apoB mRNA editing. By contrast, levels of small intestinal apoB mRNA editing were indistinguishable in wild-type and apobec-1+/- animals, suggesting that Apobec-1 is expressed in limited quantities in the liver but not in the small intestine. The apobec-1-/- mice lacked detectable levels of Apobec-1 mRNA, expressed only unedited apoB mRNA in all tissues, and contained no apoB48 in their serum, demonstrating that there is no functional duplication of this gene.

APOBEC-1 Deaminase

Fluid administration, brain edema, and cerebrospinal fluid lactate and glucose concentrations in experimental Escherichia coli meningitis.

The effect of no fluids versus liberal fluid supplementation on brain edema and cerebrospinal fluid (CSF) lactate and glucose concentrations was compared in rabbits with experimental Escherichia coli meningitis. Fluid restriction for the duration of the experiment (19 h) led to a decrease in body weight by approximately 5%, while the high fluid regimen increased body weight by approximately 5%. Infected animals developed brain edema compared with controls, but the fluid regimen had no measurable effect on the degree of edema. In contrast, fluid-restricted animals had significantly higher CSF lactate and lower CSF glucose concentrations than fluid-supplemented animals (lactate, 13.5 +/- 3.5 vs. 10.1 +/- 3.3 mmol/L; glucose, 1.89 +/- 1.39 vs. 4.11 +/- 1.39 mmol/L). These results fail to support the hypothesis that administration of large amounts of fluid in this model of gram-negative bacterial meningitis aggravates brain edema.

Animals

Hemodynamic evaluation by Doppler echocardiography of small (less than or equal to 21 mm) prostheses and bioprostheses in the aortic valve position.

To assess resting hemodynamics of an unselected group of patients with prostheses or bioprostheses sized less than or equal to 21 mm implanted into the aortic valve position during a 7-year period, 46 of 50 eligible patients were examined by Doppler echocardiography. The valves were Carpentier-Edwards (CE) supraannular 21 mm (n = 8), Medtronic-Hall (MH) 20 mm (n = 8) and 21 mm (n = 21), and the rest (n = 9) were other valves with only 1 to 3 patients in each group. Gradients, valve areas and dimensionless obstruction indexes (ratio of subvalvular/valvular velocities and velocity time integrals) were compared. By analysis of variance, gradients did not differ significantly between the CE supraannular 21 mm, the MH 20 and 21 mm prostheses (peak/mean 25 +/- 8/14 +/- 5, 31 +/- 13/16 +/- 6 and 25 +/- 10/13 +/- 5 mm Hg; p = not significant). Only 2 patients had a mean gradient greater than 25 mm Hg. The valve area was slightly larger for the MH 21 mm group compared with the CE supraannular 21 mm group (1.34 +/- 0.15 vs 1.16 +/- 0.14 cm2, p less than 0.05). The dimensionless obstruction indexes did not differ (CE supraannular 21 mm 0.36 +/- 0.07/0.40 +/- 0.07 (velocities/velocity time integrals), MH 20 mm 0.40 +/- 0.12/0.47 +/- 0.12, MH 21 mm 0.38 +/- 0.05/0.44 +/- 0.06; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin.

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Animals

MRI: a method to detect minor brain damage following coronary bypass surgery?

In order to assess the occurrence of minor focal brain lesions after coronary bypass surgery, magnetic resonance imaging (MRI) was used. Nine male patients (age 42-63) with angina pectoris were investigated at 0.5 Tesla. The investigation was performed one to seven weeks prior to the operation and one month after the operation. Before surgery, the images demonstrated more than five high intensity spots in the white matter of the brain in all but two patients. No additional spots were found after operation. This pilot study indicates that it might be difficult to use MRI to detect minor parenchymal lesions after cardiopulmonary bypass surgery.

Brain

Vascular complications of lumbar disc surgery. Case report.

Four patients were successfully treated for vascular complications associated with lumbar disc surgery, one as an emergency case and three from 1 to 3 months postoperatively. Acute complications are often identified by severe bleeding. Knowledge of the anatomy is essential for appropriate surgical repair, which may consist of patch-graft angioplasty or graft interposition. Treatment of late complications (usually arteriovenous fistula or false aneurysm) is often impeded by adhesions. Fistula repair is performed from inside the artery. Precautions against vascular complications during lumbar disc surgery are discussed.

Acute Disease

Anterior perforations in lumbar discectomies. A report of four cases of vascular complications and a CT study of the prevertebral lumbar anatomy.

Four cases of vascular complications to anterior perforations during discectomy prompted a CT study to measure lumbar disc diameters and to evaluate the prevertebral anatomy. Fifty young adults who had been referred for low-back pain and/or sciatica but had not undergone operation were included. In five additional patients, prone versus supine CT examinations were compared. Six typical configurations of the vascular anatomy could be classified to explain the type of vascular complications occurring at the L3-4 and L4-L5 disc levels. The sagittal diameter of the three lowest lumbar discs varied from 33 to 56 mm, indicating the importance of this parameter as an intraoperative guideline for the spine surgeon. Air-filled intestines were observed anterior to the L5-S1 disc predominantly in the prone position. The possible relationship between this finding and postoperative discitis is discussed.

Adult

Aortoduodenal fistula reconstructed with autogenous tissue. Case report.

Aortoenteric fistula is a rare but serious complication of aortic surgery. A case of secondary aortoduodenal fistula is presented. Treatment with closure of the fistula and removal of part of the graft was successful. The circulation was restored by autogenous saphenous vein bypass grafting.

Aortic Diseases

Transcapillary fluid balance in subcutaneous tissue of patients undergoing aortocoronary bypass with extracorporeal circulation.

Colloid osmotic pressure in plasma (COPpl) from a cubital vein and in interstitial fluid (COPif) in the subcutaneous tissue at heart level, and interstitial fluid pressure (Pif) at the same level, were measured in 18 healthy subjects and in 28 patients requiring aortocoronary bypass. Interstitial fluid was collected via subcutaneously implanted double nylon wicks and Pif was measured with the 'wick-in-needle' technique. Measurements were made preoperatively and 1 1/2 to 8 hours (mean 4 hours) after termination of extracorporeal circulation. Pif rose to 2.3 mmHg above the pre-bypass level. COPpl concomitantly fell from 22.2 to 14.4 and COPif from 12.4 to 10.1 mmHg. These changes were statistically significant. Although the relatively large COPpl drop resulted in a net rise of 3.2 mmHg in filtration pressure, the incidence of pulmonary complications was low and no subcutaneous edema was discernible. The fall in COPif and rise in Pif may be regarded as important edema-preventing mechanisms.

Adult

Thrombotic disc impediment in a Medtronic-Hall aortic valve prosthesis diagnosed by Doppler echocardiography followed by successful reoperation.

A case with impeded disc movement caused by thrombus formation in a Medtronic-Hall aortic valve prosthesis is reported. A correct diagnosis, including both mechanism and severity of the prosthesis failure, was established by Doppler echocardiography. The patient was promptly referred for surgery without invasive or other supplementary investigations.

Aortic Valve