Noninvasive assessment of arterial distensibility in adolescents using the second derivative of photoplethysmogram waveform

To clarify the clinical usefulness of the second derivative of the waveform of the fingertip photoplethysmogram (SDPTG), we examined the relationship between the pattern of the SDPTG waveform and risk factors related to atherosclerosis in 1,495 boys and girls aged 9–17 years. The fingertip photoplethysmogram and its second derivative wave were automatically recorded from the second digit of the right hand with the subjects lying in a supine position. The SDPTG waveform consisted of a, b, c and d waves in systole and an e wave in diastole. The heights of the a and d waves were measured from the baseline, and the ratio of the height of the d wave to that of the a wave (d/a ratio) was calculated. The d/a ratio had a negative correlation with the systolic (SBP) and diastolic blood pressures (DBP), atherogenic index (AI) and immunoreactive insulin concentrations (IRI) after adjustment for age. Multiple linear regression analysis revealed that the d/a ratio was associated more with body height than the risk factors for atherosclerosis in boys and girls at the growth period. The effect of sex- and height-specific cutoff values of the 10th percentile for the d/a ratio was therefore tested. The results showed that subjects with d/a ratios lower than the 10th percentile had significantly higher SBP, DBP, AI and IRI values compared to those with higher d/a ratios. These findings suggest that differences in the length of the vascular system, which are related to increases in body height, may modify the SDPTG waveform pattern during adolescence. When the body height as well as age and sex is adequately allowed for, the d/a ratio may be useful for the evaluation of arterial distensibility and for identification of individuals at an increased risk of developing atherosclerosis. Electronic Publication     

GASTRIC CANCER RETROSPECTIVELY INVESTIGATED FOR 9 YEARS AND 6 MONTHS: A CASE OF LINITIS PLASTICA

This report presents a rare case of a patient with gastric cancer whose clinical course with the development of tumor from early cancer type IIc to advanced cancer of linitis plastica was observed for 9.5 years. The cancer remained in early stage for 3 years and 8 months after the patient’s first endoscopy. At 5 years and 10 months after initial endoscopy, the lesion progressed to advanced cancer, and after 6 years and 7 months sclerotic changes in the gastric wall were detected at the lesion site. After 9 years, advanced gastric cancer of linitis plastica was present throughout the stomach. The initial stage of linitis plastica is considered to be early gastric cancer type IIc with histologically undifferentiated cancer cells. It is widely accepted that a period of 6–8 years is required for this type of cancer to develop from carcinogenesis to completion of lesions. The present case is valuable in that development from early gastric cancer type IIc to linitis plastica during approximately 10 years of follow up was clinically observed, and will contribute to knowledge of the natural history of gastric cancer.     

A trial diagnosis of latent dilated cardiomyopathy

To diagnose latent dilated cardiomyopathy (latent DCM), we performed loading echocardiography with Angiotensin II and ergometer exercise in 41 patients. Twenty-one patients were suspected of having latent DCM because of histories, of heart failure of myocarditis; 10 patients had DCM; and 10 normal persons served as controls. On angiotensin II loading, cardiac function deteriorated in the DCM group, but it was maintained in the normal controls. Nine patients in the latent DCM group showed the same pattern as normals (L1-group), and 12 did as the DCM group (L2-group). Although % fractional shortening, end-diastolic and end-systolic dimensions of the left ventricle did not differ between the L1 and L2-groups, the A/R, the ratio of the pulsed Doppler echocardiogram at the left ventricular inflow tract, was larger and the exercise change of the % fractional shortening and exercise tolerance were less in the L2-group than in the L1-group. Furthermore, the biopsy findings of the L2-group were similar to those of the DCM group in terms of myocardial degeneration, myocardial hypertrophy and interstitial fibrosis. Thus, patients in the L2-group were thought to have a risk for DCM, and were cases of latent DCM. Angiotensin II loading is thought to be useful for diagnosing such cases.     

Effect of Euro-Collins' or UW solution on the early graft function following cadaveric kidney transplantation

From November 1985 to March 1990, 55 cadaveric kidney transplants were performed under cyclosporine therapy. All kidneys were harvested from non-heart beating donors and cold stored after being flushed with EC solution (Group I, n = 27) or UW solution (Group II, n = 28). Warm ischemic time (min) in groups I and II were 7.1 +/- 3.3 and 6.9 +/- 2.3, respectively. Cold ischemic times (hr) in groups I and II were 6.9 +/- 2.4 and 8.4 +/- 2.8, respectively. Mean numbers of days for postoperative dialysis were 14.0 +/- 7.9 in group I and 7.9 +/- 5.8 in group II (p less than 0.05). One-month creatinine (mg/dl) was 2.9 +/- 2.8 in group I and 1.75 +/- 1.0 in group II (NS). One-month graft survivals (%) in groups I and II were 81.4% and 92.8%, respectively. In conclusion, UW solution has provided beneficial effect of preservation on ischemic damaged kidney and appears to be method of choice in non-heart beating cadaveric kidney transplantation.     

Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.

Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.     

Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy’s induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.     

Lumbar posterolateral fusion inhibits sensory nerve ingrowth into punctured lumbar intervertebral discs and upregulation of CGRP immunoreactive DRG neuron innervating punctured discs in rats

Degeneration of lumbar intervertebral discs is thought to be a cause of low back pain. Studies have found that a cause of discogenic low back pain is intervertebral disc inflammation and axonal growth of afferent fibers innervating the disc. Lumbar spine fusion for chronic discogenic low back pain is considered an effective procedure. However, no study has investigated the mechanism of pain relief. We did this by applying Fluoro-Gold (FG) to the ventral aspect of the L4–L5 intervertebral discs of 40 rats. We exposed the nucleus pulposus to the annulus fibrosus in a disc punctured model. Rats were divided into 4 groups. Group A: Punctured intervertebral disc with sham posterolateral fusion (PLF) (n = 10), Group B: Punctured intervertebral disc with PLF (n = 15), Group C: Normal intervertebral disc (no puncture) with PLF (n = 10), and Group D: Normal disc (no disc puncture) with sham PLF (n = 5). Four weeks after surgery, bilateral L1–L5 dorsal root ganglia (DRGs) were stained with growth-associated protein 43 (GAP43), a marker of axonal growth, and calcitonin gene-related peptide (CGRP), a neuropeptide marker of pain. Bone union was evaluated using X-ray imaging. Of the FG-labeled neurons, the proportions of GAP43- and CGRP-immunoreactive (IR) neurons in Group A were significantly higher than in Group D (P < 0.05). The proportions of GAP43- and CGRP-IR neurons in bone union rats in Group B were significantly lower than in nonunion rats in Group B and in the rats in Group A (P < 0.05). No significant differences in GAP43- and CGRP-IR neurons were observed between bone union and nonunion rats in Group C and the rats in Group D (P > 0.05). PLF is strongly related to the downregulation of GAP43 and CGRP expression. Therefore, PLF may suppress the increase of inflammatory neuropeptides and the process of axonal growth. Moreover, these results may explain, in part, the mechanism of pain relief following lumbar spinal fusion for chronic discogenic low back pain in humans.     

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease

Background

To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens.

Methods

The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively.

Results

Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements.

Conclusions

This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.