An Autopsy Case of Dermatomyositis with Rapidly Progressive Diffuse Alveolar Damage

A 47-year-old woman visited a clinic with dyspnea which had continued for two months and was followed by general fatigue and fever. Antibiotics were not effective. Edematous erythema occurred on her face, elbows, knees and feet, and she entered our hospital. A skin biopsy revealed interface dermatitis with severe edema and mucinosis in dermis. Diffuse bilateral infiltration was observed in the chest X-ray, and laboratory findings showed increased LDH, GPT, GOT and CPK. No antinuclear factor was detected. Her respiratory condition rapidly worsened, and she died eight days after hospitalization in spite of corticosteroid pulse therapy. The autopsy revealed that the main cause of death was diffuse alveolar damage (DAD). Interstitial pneumonia related to dermatomyositis is not histologically uniform; the response to the therapy depends on its histological type. The patients with dermatomyositis who have poor prognosis are clinically characterized by acute onset with general symptoms and less pronounced muscle weakness; they generally show DAD in their lungs. We need to establish a simple method for distinguishing histological types of interstitial pneumonia and adequate therapy for each one.     

Effects of Intestinal and Hepatic Metabolism on the Bioavailability of Tacrolimus in Rats

Purpose. Tacrolimus, an immunosuppressive agent, has poor and variable bioavailability following oral administration in clinical use. We investigated the contribution of intestinal metabolism to the first pass effect of tacrolimus in rats. Methods. Tacrolimus was administered intravenously, intraportally or intraintestinally to rats. Blood samples were collected over a 240-min period, and blood tacrolimus concentrations were measured. The extraction ratios of tacrolimus in the intestine and liver were investigated. In addition, the metabolism of tacrolimus in the everted sacs of the small intestine was examined. Results. The rate of absorption of tacrolimus in the intestine was rapid, and tacrolimus was almost completely absorbed after intestinal administration. The bioavailability of tacrolimus was about 40% and 25% after intraportal and intraintestinal administration, respectively, indicating that tacrolimus is metabolized in both the intestine and the liver. In addition, tacrolimus was significantly metabolized in the everted sacs of the rat intestine. Conclusions. The present study suggested that the metabolism of tacrolimus in the intestine contributes to its extensive and variable first pass metabolism following the oral administration.     

Mechanical power during maximal treadmill walking and running in young and elderly men

This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [69.4 (5.0) years] and 50 young [24.3 (3.4) years] men. The mean mechanical power over a period of time covering six steps, during which the belt velocity peaked and then kept almost plateau, was determined as a performance score in each of maximal walking (WP) and running (RP). In terms of the value relative to body mass, the relative difference between the two age groups was greater for RP (61.7%) than for WP (21.4%) or isometric knee extension (34.1%) and flexion torque (43.8%). In the two groups, WP was significantly (P<0.05) correlated to knee extension (r=0.582 for the elderly and r=0.392 for the young) and flexion torque (r=0.524 for the elderly and r=0.574 for the young). Similarly, RP was also significantly (P<0.05) correlated to knee extension (r=0.627 for the elderly and r=0.478 for the young) and flexion torque (r=0.500 for the elderly and r=0.281 for the young). In these relationships, the WP adjusted statistically by thigh muscle torque was similar in the two age groups. However, the corresponding value for RP was significantly higher in the young than in the elderly. The findings here indicate that: (1) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking, and (2) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups, the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque.     

Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review

Stenosis at the graft–vein junction caused by intimal hyperplasia (IH) is the major cause of failure of vascular access grafts used for hemodialysis. There is a strong relationship between hemodynamic factors and formation of IH. The hemodynamic pattern and the location of IH are different in arterial bypass grafts (ABGs) compared with arteriovenous grafts (AVGs). In an ABG, end-to-side anastomosis of the expanded polytetrafluoroethylene graft and artery produces hemodynamic changes around the junction. IH develops at the arterial floor and the toe and heel of the distal anastomosis. Low shear stress and oscillating shear forces at the arterial floor and the heel plus a high wall sheer stress (WSS) gradient at the toe probably promote IH development. Compliance mismatch between the graft and artery causes turbulence that may contribute to IH formation. The blood flow rate in AVGs is 5–10 times greater than that in ABGs. High flow causes turbulence that injures endothelial cells and eventually results in IH. The peak WSS in AVGs is about 6N/m², much higher than that in ABGs. Excessively high WSS may effect IH formation in AVGs. Several venous cuff or patch anastomotic designs have been used in attempts to regulate hemodynamic factors in grafts. In ABGs, these designs appear to help decrease IH formation. In AVGs, however, they generally have not improved patency rates. In a high-flow system such as an AVG, more drastic changes in anastomotic design may be required.     

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(–273)C (P=0.0074), C(–297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(–273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(–273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(–273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.     

GIANT CELL CARCINOMA OF THE PANCREAS

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67-year-old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.     

Specifically associated PCR products probed by coincident detection of two-color cross-correlated fluorescence intensities in human gene polymorphisms of methylene tetrahydrofolate reductase at site C677T: a novel measurement approach without follow-up mathematical analysis

Whole blood samples of known methylene tetrahydrofolate reductase (MTHFR) genotypes from 24 individuals were examined at site C677T. Their amplified DNA products were assessed by two-color fluorescence cross-correlation measurements and agarose gel electrophoresis/capillary gel electrophoresis. DNA subpopulations were identified which were not associated with the proper genotype by primer combinations and cycling conditions called multiplexes. We confirmed that DNA analysis by two-color fluorescence cross-correlation measurements allowed the detection of fluorescence signals specifically associated with the proper genotypes in a mixture of amplified nontarget DNA molecules without DNA sizing. The measurement approach does not require complex, follow-up mathematical analysis and is applicable to any single nucleotide polymorphisms. The simple immunogenetic model showed how the approach works to reveal specific DNA target by preventing detection of nontarget DNA. Under those experimental conditions, a new ultrasensitive, and specific method for clinical immunologists is born.     

Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome

We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.