Measurement of intrahepatic shunt using Rutland method

Intrahepatic shunt ratio was calculated from the fraction of the uptake constant and the blood background, analyzing the data of 99mTc-(Sn)-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) hepatobiliary imaging by Rutland method. Shunt flow and total hepatic blood flow (THBF) were also calculated from the values for the effective hepatic blood flow (EHBF) estimated from the blood clearance technique. In 15 cases of normal volunteer, the average of the shunt ratio, shunt flow, and THBF were 18.4 +/- 5.4 (S.D.)%, 137.8 +/- 49 ml/min, and 753 +/- 83.2 ml/min, respectively. In 8 cases of chronic hepatitis, the values were 35.2 +/- 2.6%, 276 +/- 55.4 ml/min, and 794.1 +/- 119.4 ml/min, respectively. In 12 cases of liver cirrhosis, the values were 51.4 +/- 12.6%, 353.9 +/- 141.3 ml/min, and 685.6 +/- 174.8 ml/min, respectively. In cases of chronic hepatitis and liver cirrhosis, in comparison with normal cases, the values for the shunt ratio and shunt flow were significantly increased (p less than 0.001) and those for EHBF were significantly decreased (p less than 0.001), but those for THBF were not significantly altered. There was a significant inverse correlation between the shunt ratio and EHBF (r = -0.842) in all 35 cases. This method is considered to be useful for differential diagnosis, estimation of the grade of the diseases, and evaluation of pathophysiology of various diffuse liver diseases.     

VISUOMOTOR PERFORMANCE OF NORMAL AND CLUMSY CHILDREN. II: ARM-TRACKING WITH AND WITHOUT VISUAL FEEDBACK

Tracking performance was investigated in normal and clumsy children in two age-groups, six to seven and 10 to 11 years. Target signals moving unpredictably along a straight line had to be tracked, both with and without visual feedback. Performance was described in three ways: (1) performance in the low-frequency range (LF); (2) the delay between target signal and tracking movement (DL); and (3) a measure of tracking quality or over-all similarity in the shape of target signal and tracking movement (Q). Clumsy children in both age-groups had a lower tracking quality (Q) and longer delay (DL) than the normal children. Disturbances in the regulation of attention seemed to affect tracking performance, particularly of the six- to seven-year-old clumsy children. There was no significant difference between normal and clumsy children in the effect of visual feedback on tracking performance. This suggests that clumsiness is not linked to disturbance of integration of visual feedback information and motor processes.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Insulin resistance is associated with circulating fibrinogen levels in nondiabetic patients receiving peritoneal dialysis.

BACKGROUND: Insulin resistance (IR) and inflammation are associated with increased risk of cardiovascular disease in the general population. Continuous glucose absorption in peritoneal dialysis (PD) may induce hyperglycemia and hyperinsulinemia. METHODS: We evaluated IR in nondiabetic patients receiving PD, and analyzed the association between IR and systemic inflammation biomarkers by performing a cross-sectional study on ambulatory dialysis. A total of 25 nondiabetic patients receiving PD and 25 healthy individuals, matched for gender, age, and body mass index (BMI), were included. The PD group was composed of 11 men and 14 women, with a mean age of 47 +/- 14 years and mean BMI of 25.5 +/- 4.7 kg/m(2). The control group was composed of 10 men and 15 women, with a mean age of 45 +/- 12 years and BMI of 24.0 +/- 2.8 kg/m(2). RESULTS: IR was evaluated by the homeostasis model assessment method (HOMA-IR). Inflammation was assessed through high-sensitivity C-reactive protein (CRP) and fibrinogen. Body composition and truncal fat were evaluated by dual energy x-ray absorptiometry. HOMA-IR was significantly higher (P < .0001) in subjects receiving PD (4.9, range: 2.3-9.3 mmol/L x muU/mL) compared with healthy subjects (1.2, range: 0.4-4.8 mmol/L x muU/mL). As expected, compared with controls, patients receiving PD had significantly higher levels of insulin (26.5 +/- 7.5 muU/mL vs 6.3 +/- 3.4 muU/mL; P < .0001), CRP (6.3, range: 0.3-61.1 mg/L vs 2.4, range: 0.6-5.9 mg/L; P = .001), and fibrinogen (379 +/- 101 mg/dL vs 268 +/- 66 mg/dL; P < .0001). However, there were no significant differences in body and truncal fat mass between the groups. A significant correlation between HOMA-IR and fibrinogen (Rho = 0.48; P = .01) was observed. However, no correlation was found between HOMA-IR and CRP. Also, no significant correlations were found between HOMA-IR and body fat mass (Rho = 0.11), and between HOMA-IR and truncal fat mass (Rho = 0.19). CONCLUSIONS: Patients receiving PD demonstrate a state of IR that is associated with high circulating levels of fibrinogen. This suggests that hyperfibrinogenemia may be involved in the pathogenesis of IR in this setting.     

Diagnostic accuracy of fetal renal pelvis anteroposterior diameter as a predictor of uropathy: a prospective study.

OBJECTIVE: The purpose of this study was to assess the accuracy of prenatal ultrasound measurement of anteroposterior renal pelvis diameter (APD) to discriminate between significant uropathy and idiopathic renal pelvis dilatation. METHODS: One-hundred-and-three neonates who were found to have fetal renal pelvis dilatation, defined as presence of an APD > or = 5 mm, underwent systematic investigation for uropathies and were prospectively followed. An ultrasound scan was performed after the first week of postnatal life and all infants underwent a voiding cystourethrogram. Neonates with an APD larger than 10 mm underwent renal scintigraphy. Ultrasound scans, clinical examination and laboratory reviews were scheduled at 6-month intervals. Receiver-operating characteristics (ROC) curves were constructed to determine the best cut-offs for APD to identify renal units with significant uropathy as well as those requiring surgical intervention. Significant uropathy was defined as the presence of well-established urinary tract abnormalities or when there was abnormal renal scintigraphy. RESULTS: The estimated area under the curve for APD was 0.900 (95% CI, 0.841-0.942) indicating excellent power to discriminate between idiopathic pelvis dilatation and significant uropathy. The sensitivity and specificity for the 7.5 mm cut-off point were 97.9% and 40.6%, respectively. To identify infants who required surgical intervention, the calculated area under the curve was 0.953 (95% CI, 0.908-0.980). CONCLUSION: Our results suggest that measurement of APD is an excellent test to identify fetuses with significant uropathy, as well as those requiring postnatal intervention.     

Cuff pressure in intratracheal tubes. Evaluation of the new Mallinckrodt-Brandt model

Cuff pressure of endotracheal tubes increases to dangerous levels during anesthesia with nitrous oxide. In a small clinical study the Authors conclude that Mallinckrodt-Brandt endotracheal tubes are the only "low pressure" tubes available at the moment.     

PCR amplification introduces errors into mononucleotide and dinucleotide repeat sequences.

The polymerase chain reaction (PCR) is used universally for accurate exponential amplification of DNA. We describe a high error rate at mononucleotide and dinucleotide repeat sequence motifs. Subcloning of PCR products allowed sequence analysis of individual DNA molecules from the product pool and revealed that: (1) monothymidine repeats longer than 11 bp are amplified with decreasing accuracy, (2) repeats generally contract during PCR because of the loss of repeat units, (3) Taq and proofreading polymerase Pfu generate similar errors at mononucleotide and dinucleotide repeats, and (4) unlike the parent PCR product pool, individual clones containing a single repeat length produce no "shadow bands". These data demonstrate that routine PCR amplification alters mononucleotide and dinucleotide repeat lengths. Such sequences are common components of genetic markers, disease genes, and intronic splicing motifs, and the amplification errors described here can be mistaken for polymorphisms or mutations.     

Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile

In addition to the two large clostridial cytotoxins (TcdA and TcdB), some strains of Clostridium difficile also produce an actin-specific ADP-ribosyltransferase, called binary toxin CDT. We used a PCR method and Southern blotting for the detection of genes encoding the enzymatic (CDTa) and binding (CDTb) components of the binary toxin in 369 strains isolated from patients with suspected C. difficile-associated diarrhea or colitis. Twenty-two strains (a prevalence of 6%) harbored both genes. When binary toxin production was assessed by Western blotting, 19 of the 22 strains reacted with antisera against the iota toxin of C. perfringens (anti-Ia and anti-Ib). Additionally, binary toxin activity, detected by the ADP-ribosyltransferase assay, was present in only 17 of the 22 strains. Subsequently, all 22 binary toxin-positive strains were tested for the production of toxins TcdA and TcdB, toxinotyped, and characterized by serogrouping, PCR ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis. All binary toxin-positive strains also produced TcdB and/or TcdA. However, they had significant changes in the tcdA and tcdB genes and belonged to variant toxinotypes III, IV, V, VII, IX, and XIII. We could differentiate 16 profiles by using typing methods, indicating that most of the binary toxin-positive strains were unrelated.