An evaluation of methods to decrease the availability of inorganic sulphate for sulphate conjugation in the rat in vivo

The concentration of inorganic sulphate in serum of the rat (about 0.9 mM) could be lowered in the following three different ways. (1) Oral administration of sodium chloride (8 mmol/kg) decreased serum sulphate within 2 hr to 0.5 mM. Eight hours after administration serum sulphate had returned to the control level. (2) Feeding of a low-protein diet (8 per cent casein, without supplements of sulphur-containing amino acids or inorganic sulphate salts) reduced urinary sulphate excretion in 2 days to 10 per cent of control. Concomitantly, serum sulphate was decreased to half the control level. (3) Paracetamol (1.0 or 1.5 mmol/kg, orally), a substrate of sulphation, reduced serum sulphate within 3 hr to 30 per cent of control. Eight hours after administration the sulphate concentration tended to rise again. Fasting initially increased serum sulphate; after 3 days of fasting still considerable amounts of inorganic sulphate were excreted in urine (50–70 per cent of control). Even after 3 days serum sulphate was not yet significantly decreased below control. Lowering of the serum sulphate concentration results in a decreased availability of inorganic sulphate.Sulphation of a high dose of phenol (266 μmol/kg) was decreased at a serum concentration of sulphate of 0.3 mM, presumably because sulphate was depleted by the high dose of phenol. Feeding the low-protein diet, however, caused no decrease in sulphation at a tracer dose of [¹⁴C]-phenol (1.25 μmol/kg), while paracetamol pretreatment did cause a decrease in the fraction of the dose that became sulphated, probably because remaining unconjugated paracetamol competed with phenol for sulphation; the tracer dose of [¹⁴C]-phenol did not further deplete sulphate. The findings are discussed in relation to implications for the toxicity of many xenobiotics that are eliminated as sulphate conjugates.     

MR imaging of the wrist: comparison between 1.5- and 3-T MR imaging--preliminary experience

Institutional review board approval and informed consent were obtained from 25 healthy volunteers and 15 consecutive patients with chronic wrist pain or suspected carpal mass, and 1.5- and 3-T magnetic resonance (MR) imaging of the wrist was prospectively performed with comparable sequence parameters and surface coils of the same geometric design. Imaging protocols at both field strengths included a T1-weighted spin-echo sequence, two intermediate-weighted fast SE sequences with different echo times and with and without fat saturation, and a three-dimensional fast field-echo sequence. The contrast-to-noise ratio (CNR) between muscle and bone and between bone and cartilage was calculated for both field strengths. The visibility of various anatomic structures, including the triangular fibrocartilage complex, carpal ligaments, nerves, and cartilage, was analyzed with a four-point grading scale. CNRs were significantly higher on 3-T MR images than on 1.5-T MR images (P < .001; analysis of variance) for all sequences. Visibility of the triangular fibrocartilage complex and intercarpal ligaments and cartilage was significantly better on 3-T MR images than on 1.5-T MR images (paired sign test).     

Parallel imaging at high field strength: synergies and joint potential

MRI faces fundamental limitations in terms of sensitivity and speed. These limitations can be effectively tackled by the transition to higher field strengths and parallel imaging technology. Owing to largely independent physics, the two approaches can be readily combined. Considering the specific advantages and disadvantages of high field strength and parallel imaging, it is found that the combination is particularly synergistic. In the joint approach, the two concepts play different roles. Higher field strength acts as a source of higher baseline signal-to-noise ratio (SNR), while parallelization acts as a means of converting added SNR into a variety of alternative benefits. This interplay holds promise for a broad range of clinical applications, as recently illustrated by several imaging studies at 3 T. As a consequence, clinical MRI at 3 T and higher is expected to rely more on parallel acquisition than at lower field strength. The specific synergy with parallel imaging may even make 3 T the field strength of choice for a range of exams that conventionally work best at 1.5 T or less.     

Incisional hernia after repair of wound dehiscence: incidence and risk factors

The true incidence of incisional hernia after wound dehiscence repair remains unclear because thorough long-term follow-up studies are not available. Medical records of all patients who had undergone wound dehiscence repair between January 1985 and January 1999 at the Erasmus University Medical Center Rotterdam were reviewed. Long-term follow-up was performed by physical examination of all patients in February 2001. One hundred sixty-eight patients underwent wound dehiscence repair. Of those, 42 patients (25%) died within 60 days after surgery. During a median follow-up of 37 months (range, 3-146 months), 55 of the remaining 126 patients developed an incisional hernia. The cumulative incidence of incisional hernia was 69 per cent at 10 years. Significant independent risk factors were aneurysm of the abdominal aorta (10-year cumulative incidence of 84%, P = 0.02) and severe dehiscence with evisceration (10-year cumulative incidence of 78%, P = 0.01). Wound dehiscence repair by interrupted sutures had no better outcome than repair by continuous sutures. Suture material did not influence incidence of incisional hernia. Incisional hernia develops in the majority of patients after wound dehiscence repair, regardless of suture material or technique. Aneurysm of the abdominal aorta and severe dehiscence with evisceration predispose to incisional hernia.     

Detrimental effects of overstuffing or understuffing with a radial head replacement in the medial collateral-ligament deficient elbow

BACKGROUND: Comminuted radial head fractures associated with an injury of the medial collateral ligament can be treated with a radial head implant. We hypothesized that lengthening and shortening of the radial neck would alter the kinematics and the pressure through the radiocapitellar joint in the medial collateral ligament-deficient elbow. METHODS: The effects of lengthening (2.5 and 5 mm) and shortening (2.5 and 5 mm) of the radial neck were assessed in six human cadaveric upper extremities in which the medial collateral ligament had been surgically released. The three-dimensional spatial orientation of the ulna was recorded during simulated active motion from extension to flexion. Total varus-valgus laxity and ulnar rotation were measured. Radiocapitellar joint pressure was assessed with use of pressure-sensitive film. RESULTS: Radial neck lengthening or shortening of >/=2.5 mm significantly changed the kinematics in the medial collateral ligament-deficient elbow. Lengthening caused a significant decrease (p < 0.05) in varus-valgus laxity and ulnar rotation (p < 0.05), with the ulna tracking in varus and external rotation. Shortening caused a significant increase in varus-valgus laxity (p < 0.05) and ulnar rotation (p < 0.05), with the ulna tracking in valgus and internal rotation. The pressure on the radiocapitellar joint was significantly increased after 2.5 mm of lengthening. CONCLUSIONS: This study suggests that accurate restoration of radial length is important and that axial understuffing or overstuffing of the radiohumeral joint by >/=2.5 mm alters both elbow kinematics and radiocapitellar pressure. CLINICAL RELEVANCE: This in vitro cadaver study indicates that a radial head replacement should be performed with the same level of concern for accuracy and reproducibility of component position and orientation as is appropriate with any other prosthesis.     

Body movement and physical activity energy expenditure in children and adolescents: how to adjust for differences in body size and age

BACKGROUND: Physical activity data in children and adolescents who differ in body size and age are influenced by whether physical activity is expressed in terms of body movement or energy expenditure. OBJECTIVE: We examined whether physical activity expressed as body movement (ie, accelerometer counts) differs from physical activity energy expenditure (PAEE) as a function of body size and age. DESIGN: This was a cross-sectional study in children [n = 26; (+/-SD) age: 9.6 +/- 0.3 y] and adolescents (n = 25; age: 17.6 +/- 1.5 y) in which body movement and total energy expenditure (TEE) were simultaneously measured with the use of accelerometry and the doubly labeled water method, respectively. PAEE was expressed as 1) unadjusted PAEE [TEE minus resting energy expenditure (REE); in MJ/d], 2) PAEE adjusted for body weight (BW) (PAEE. kg(-1). d(-1)), 3) PAEE adjusted for fat-free mass (FFM) (PAEE. kg FFM(-1). d(-1)), and 4) the physical activity level (PAL = TEE/REE). RESULTS: Body movement was significantly higher (P = 0.03) in children than in adolescents. Similarly, when PAEE was normalized for differences in BW or FFM, it was significantly higher in children than in adolescents (P = 0.03). In contrast, unadjusted PAEE and PAL were significantly higher in adolescents (P < 0.01). CONCLUSIONS: PAEE should be normalized for BW or FFM for comparison of physical activity between children and adolescents who differ in body size and age. Adjusting PAEE for FFM removes the confounding effect of sex, and therefore FFM may be the most appropriate body-composition variable for normalization of PAEE. Unadjusted PAEE and PAL depend on body size.     

The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase

Thymidine phosphorylase (platelet-derived-endothelial-cell-growth-factor) catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate, activates 5'-deoxy-5-fluorouridine (5'DFUR) and inactivates trifluorothymidine (TFT). The effect of 5'DFUR and TFT with or without a specific thymidine phosphorylase inhibitor (TPI) on thymidine phosphorylase mRNA, protein expression and activity was studied, in three human colon cancer cell lines, WiDR, HT29 and Lovo exposed for 72 h at IC50 concentrations. In Lovo cells TFT plus TPI only increased thymidine phosphorylase-protein expression 1.7-fold; 5'DFUR and TFT treatment increased thymidine phosphorylase mRNA levels 5- and 1.4-fold, respectively. In WiDR cells, 5'DFUR plus TPI significantly decreased thymidine phosphorylase-protein. TFT and TFT plus TPI increased thymidine phosphorylase-protein 2- and 3-fold, respectively. TPI and 5'DFUR decreased thymidine phosphorylase-mRNA levels significantly. In HT29 cells, 5'DFUR and 5'DFUR plus TPI decreased both thymidine phosphorylase-protein and thymidine phosphorylase-mRNA. In all cell lines 5'DFUR and TFT did not affect thymidine phosphorylase activity, but treatment with TPI (alone or in combination) eliminated thymidine phosphorylase activity. This demonstrated that regulation is drug and cell line dependent.