Familial predisposition and clustering for juvenile lumbar disc herniation.

The siblings and parents of 40 patients (cases) with lumbar disc herniation (aged 18 years or younger) who underwent surgery at the Department of Orthopaedics at Toyama Medical and Pharmaceutical University Hospital between 1976 and 1990 were examined for incidence of lumbar disc herniation. A total of 120 randomly sampled, age- and sex-matched patients (controls) who were hospitalized during the same period due to extraspinal diseases also were studied in the same manner. A survey of the occurrence of definite lumbar disc herniation was carried out that included 75,237 students in elementary, junior high, and senior high schools in Toyama Prefecture, Japan, covering a mean period of 3 years and 4 months. The incidence of surgically treated lumbar disc herniation among people aged 18 years or younger was calculated, and the expected value of disc herniation was obtained in an age-specific manner, on the basis of the age distribution of encumbrances in the above case-control study. The encumbrances of 18-year-old or younger patients with lumbar disc herniation showed familial predisposition, with an odds ratio of 5.61 in comparison to the controls. It was suggested that there is familial clustering of lumbar disc herniation among the encumbrances of 18-year-old or younger patients with lumbar disc herniation.     

Factors influencing exercise tolerance in patients with myocardial infarction as elucidated by Tl-201 myocardial scintigraphy

Measurements of O2 consumption during treadmill exercise tests and Tl-201 myocardial scintigraphy were performed in 17 cases of myocardial infarction to elucidate O2 consumption at an anaerobic threshold ATVO2 as an adequate index of exercise tolerance, and the scintigraphic indices influencing the exercise tolerance. ATVO2 was obtained using the method of Wasserman and Davisand corrected by body weight. The scintigraphic indices such as the location, extent (residual myocardium), and severity (% uptake) of myocardial infarction were obtained from SPECT and bull's eye displays on Tl-201 myocardial scintigraphy. ATVO2 was correlated with theoretical VO2max as obtained by the predicted maximal heart rate (r = 0.56, p less than 0.01) and with left ventricular ejection fraction as obtained by radionuclide left ventriculography (r = 0.59, p less than 0.01). There was no significant difference between ATVO2 in cases of anterior wall infarction and those of inferior (and/or lateral wall) infarction. There was no significant correlation between % uptake and ATVO2. However, the residual myocardium showed a significant correlation with ATVO2 (r = 0.61, p less than 0.01). In conclusion, 1) ATVO2 is an adequate index of exercise tolerance and reflects cardiac function. 2) The extent of the residual myocardium is most strongly influenced by ATVO2 among the indices of myocardial damage as obtained by Tl-201 myocardial scintigraphy.     

Distribution of a Brain-specific Proteoglycan, Neurocan, and the Corresponding mRNA During the Formation of Barrels in the Rat Somatosensory Cortex

Neurocan is a developmentally regulated chondroitin sulphate proteoglycan in the rat brain. In the present study, spatiotemporal patterns of expression of neurocan and the corresponding mRNA were examined in the developing cortical barrel field of the rat brain by using a monoclonal antibody that was highly specific to neurocan and a riboprobe for a portion of the mRNA. Immunohistochemical analysis revealed that neurocan was distributed throughout the cerebral cortex during early postnatal development but was excluded from the centres of cortical barrels at the time of entry and arborization of thalamocortical axons. At this developmental stage, expression of neurocan mRNA was shown by in situ hybridization to be down-regulated in the barrel centres. When a row of whisker follicles was laser-cauterized on postnatal day 1, the pattern of expression of neurocan was disturbed in the row of barrels that corresponded to the lesioned whisker follicles in the contralateral somatosensory cortex. From these observations, it appears that neuronal stimuli through early thalamocortical fibres from the sensory periphery cause reduced expression of neurocan mRNA in neurocan-producing cells in the presumptive barrel centres. Our findings also suggest that the pattern of distribution of neurocan in early postnatal barrel fields may be due mainly to the down-regulation of expression of neurocan mRNA.     

A copper chelating agent suppresses carbonyl stress in diabetic rat lenses

To clarify whether transition metals are involved in carbonyl stress in diabetic tissues, we observed the effects of a metal chelating agent, trientine (TE) hydrochloride on the levels of methylglyoxal (MG), 3-deoxyglucosone (3-DG), advanced glycation end products, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and polyol pathway metabolites along with semicarbazide-sensitive amine oxidase (SSAO) enzyme activity in lenses from streptozotocin-induced diabetic rats. Lens MG and 3-DG levels were significantly higher in diabetic rats than nondiabetic controls, and TE significantly restored the increase of these compounds. Lens argpyrimidine was also increased in diabetic rats as compared with controls and was significantly reduced by TE. Lens SSAO activity and 8-OHdG were also significantly elevated in diabetic rats, and TE suppressed both of them, whereas TE showed no effect on the polyol pathway metabolites. The results indicate that transition metals play a significant role in the formation of MG and 3-DG via oxidative stress and SSAO activity.     

Exencephaly induction by valproic acid in the genetic polydactyly/arhinencephaly mouse, Pdn/Pdn

Non-treated homozygous polydactyly/arhinencephaly (Pdn/Pdn) mouse fetuses exhibited exencephaly in 16.7% of cases. Treatment of Pdn/Pdn mice with 350 mg/kg of valproic acid (VPA) on days 8.5 and 9.5 of gestation increased the rate of exencephaly to 66.7%. The responsible gene for the Pdn mouse phenotype has been determined to be Gli3, and the suppression of Gli3 gene expression has been documented in Pdn/Pdn embryos. We investigated how the sonic hedgehog (Shh) and Fgf8 genes, the correlated genes of Gli3, are expressed in the VPA-treated exencephalic Pdn/Pdn embryos on day 10 of gestation, using whole mount in situ hybridization (WISH) and real-time PCR methods. We could not detect any alterations in Shh expression by real-time PCR, or WISH in the non-treated Pdn/Pdn and VPA-treated exencephalic Pdn/Pdn embryos. Altered Fgf8 expression patterns were observed in the commissural plate and dorsal isthmal neuroepithelium in the non-treated Pdn/Pdn embryos. We speculated that the altered expression of Fgf8 might be the result of down-regulation of Gli3 in Pdn/Pdn embryos. Fgf8 gene expression in the commissural plate and dorsal isthmal neuroepithelium exhibits wide or altered signal patterns in the VPA-treated exencephalic Pdn/Pdn embryo. From these findings, it was suggested that down-regulation of Gli3 gene expression induced the altered expression of Fgf8 in the Pdn/Pdn embryos, and that VPA treatment accelerated the alterations of Fgf8 gene expression in the Pdn/Pdn embryos. It was further speculated that altered expression of Fgf8 in the commissural plate may be the fundamental cause of exencephaly, and that the synergistic effect between gene and drug shown in this experiment may explain the differences of sensitivity in the side-effects of the drug.     

Study of the usefulness of large intestine screening inspections using multi-slice CT (MSCT)

CT-colonography (CT-C), a new diagnostic imaging technique for cancer of the large intestine--which is increasing rapidly owing to westernized eating habits--has advanced from the developmental stage to the stage of practical application, thanks to progress in MSCT and workstation development. Therefore, based on the results of CT-C application using 16 lines of MSCT to a screening test, we reviewed the usefulness of CT-C in our clinic. We supplemented defective depiction, and found that change of position was effective for virtual image exclusion. We consider that CT-C can support diagnosis if the target of screening tests is a polypoid lesion of more than 6 mm. In addition, it is expected that the number of examinations performed during office visits will increase because of the decreased invasiveness of the procedure, its lack of pain, and its ability to provide early lesion detection.     

Severe hyperreninemic hypertension associated with spontaneous renal cholesterol crystal embolization

A 70-year-old man was admitted because of severe hypertension and renal insufficiency. Marked elevation in plasma renin activity (PRA; 34.2ng/ml per h) was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and panperitonitis, went into shock, and died. An autopsy revealed severe atherosclerosis with marked ulceration in the abdominal aorta. Renal histology showed multiple cholesterol crystal embolization (CCE) associated with infarction. Cholesterol crystals were also detected in the vessels of the gastrointestinal system, including the liver, stomach, colon, and pancreas. Although not common, spontaneous CCE should be considered in elderly patients who present with abrupt onset of severe hypertension associated with renal insufficiency. The most important finding in this patient was severe hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system is the suggested mechanism for the hypertension in renal CCE, we could not find any reported case of renal CCE with hyperreninemia. It is reasonable to consider that severe hyperreninemia might be overlooked in renal CCE. PRA should be measured in patients with renal CCE, because it may give important information for selecting antihypertensive agents and improving the prognosis. To clarify this possibility, an accumulation of similar cases is necessary.