Familial Mitochondrial Encephalomyopathy with Stroke-like Episodes and Episodic Disturbances of Consciousness: A Study of Pedigree Including Three Generations with Multisystemic Abnormalities

Abstract: We report here two cases in a family with pleomorphic clinical features which include mitochondrial myopathy, encephalopathy, stroke-like episodes, episodic disturbances of consciousness and other multisystemic abnormalities. The other signs observed in multisystemic abnormalities were ophthalmoplegia, short stature, diabetes mellitus, diabetes insipidus, renal dysfunction, optic atrophy, retinal degeneration, impairment of hearing and mental retardation or deterioration. A symptomatological variation was observed in cases in the same family. It is suggested that these widely varying symptoms may be expressions caused by a common biochemical defect which involves different tissuesin different individuals in the family. The syndromes observed in the present cases were compared with other possibly-related mitochondrial encephalomyopathies.     

Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model

To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of circulatory and respiratory responses between supplementary epidural buprenorphine and eptazocine administration during and immediately after total intravenous anesthesia

Opioid supplements are often required in total intravenous anesthesia (TIVA). Most ϰ-opiate receptors are found in the spinal cord, wherea μ-opiate receptors are widespread throughout the brain and spinal cord. Buprenorphine has a strong μ-action with a minute ϰ-action, while eptazocine stimulates ϰ-receptors only. From these, epidural eptazocine is expected to exert strong spinal analgesia by ϰ-stimulation without μ-action, which produces circulatory and respiratory depression. Therefore, the clinical effects of epidural opioids on circulation, respiration, and analgesia were compared. Continuous epidural administration of eptazocine or buprenorphine was combined with TIVA in patients scheduled for elective abdominal surgery. Epidural opioid administration was continued throughout and for 72h after anesthesia. A significant analgesic effect (P<0.01) of epidural eptazocine without circulatory and respiratory depression was observed. With epidural buprenorphine, circulatory and respiratory depression during and immediately after anesthesia were significant (P<0.05). These results suggest that medullary μ-stimulation by an epidural opioid induces circulatory (hypervagotonicity and hypervagosensitivity) and respiratory depression, while ϰ-stimulation produces only minimal effects on circulatory and respiratory systems.     

Tolerance to N2O-induced alterations in somatosensory evoked potentials

The effect of nitrous oxide (N2O) on somatosensory evoked potentials from the cortical (CEP) and spinal cord (SCP) regions in response to forepaw stimulation was studied in ketamine-anesthetized and mechanically ventilated rats. The CEP was recorded from the skull over the contralateral somatosensory area; the SCP was recorded from the supraspinous ligament at C57-6 and L1-2 levels of the spine. Rats were exposed to 70% N2O for 5 h, whereupon N2O was withdrawn for 2 h. Thereafter, the rats were re-exposed to N2O for 10 min. The N13-P21 component of the CEP, the slow positive wave (P2) of the segmental SCP, and the heterosegmental positive cord dorsum potential (HSP) were significantly suppressed by N2O, while the large negative (N1) component of the segmental SCP remained unchanged. A partial recovery of the CEP and HSP was observed during the 5 h of N2O anesthesia, while significant recovery of the P2 component of the SCP was not observed. The withdrawal from N2O following 5 h exposure caused an augmentation of the CEP (When compared to the control values). Re-exposure of rats to N2O again caused the suppression of these potentials as in the initial exposure. The results suggest that the phenomenon of tolerance to N2O in terms of evoked potentials develops within 5 h in the brain but not in the spinal cord.     

Conserved tRNA gene cluster in starfish mitochondrial DNA

Summary Partial sequencing of mtDNA from four long-diverged species of starfish reveals the existence of a conserved cluster of 13 tRNA genes, organized in a manner similar to that of the tRNA cluster of sea urchin mtDNA, but located at a position distant from the presumed replication origin. These findings suggest that a clustered organization of tRNA genes may have been present in the ancestral mitochondrial genome, and raise the possibility that tRNAs may have catalyzed the dispersal rather than the accumulation of the genes which encode them.     

Tumor necrosis factor-alpha in the placenta is not elevated in pre-eclamptic patients despite its elevation in peripheral blood

PROBLEM: Tumor necrosis factor-alpha (TNF-alpha) is present in human placental and uterine cells at the early and late stages of gestation and promotes the regulation of trophoblast growth and invasion. We evaluated whether TNF-alpha levels in the placenta and blood of pre-eclamptic women differed from those with normal pregnancies. METHOD OF STUDY: The subjects were 39 pregnant women carrying single fetuses (21 normal-pregnant and 18 pre-eclamptic patients). Their average gestational age at entry was 38-39 weeks. Peripheral blood was collected before the onset of labor and separated serum was stored at -20 degrees C. A tissue segment of the placenta was cut and frozen in liquid nitrogen immediately after delivery at -80 degrees C. The frozen placental tissue was added to phosphate-buffered saline. The tissue was fully homogenized and centrifuged. Separated supernatant was stored at -80 degrees C. TNF-alpha levels in separated serum and TNF-alpha and total protein (TP) levels in separated supernatant were measured. The presence of TNF-alpha in the placenta was evaluated by immunohistochemistry in five pre-eclamptic and five normal-pregnant patients. RESULTS: Serum TNF-alpha levels were higher in pre-eclampsia than in normal pregnancies. However, TNF-alpha/TP levels in the placenta did not differ significantly between the two groups. As for TNF-alpha immunostaining of trophoblastic cells in the placenta, it was weak in three and moderate in two of the normal pregnancies, while it was absent in two, weak in one, and moderate in two in the pre-eclampsia group. CONCLUSIONS: We demonstrated no significant increase in TNF-alpha/TP levels in the placenta in pre-eclampsia despite a significant increase in serum TNF-alpha levels. There was no strong immunostaining for TNF-alpha detected by immunohistochemistry in the pre-eclampsia group. These findings suggest that TNF-alpha in the placenta is not a key cytokine to interfere with normal trophoblast invasion into the myometrium in pre-eclampsia, and that sources other than the placenta may contribute to the elevated levels of TNF-alpha found in the circulation of pre-eclamptic patients.     

Pulmonary hypertension due to tumor emboli: A report of three autopsy cases with morphological correlations to radiological findings

Three cases of pulmonary hypertension caused by tumor emboli to the lungs are described. Two of the three cases had a clinical diagnosis of pulmonary thromboembolism until surgical embolectomy, and the other had a diagnosis of primary pulmonary hypertension. Autopsy disclosed chondrosarcoma, choriocarcinoma and gastric cancer as the primary tumors, respectively. Pulmonary vascular obstruction due to tumor embolism leading to pulmonary hypertension is a previously rare clinical entity, and obstructed pulmonary vessels are believed to tend to be small vessels. We compared the autopsy and radiological findings and concluded that pulmonary tumor embolism involved not only the small peripheral arteries but also the segmental and/or lobar arteries.     

Use of an Enrichment Broth Cultivation-PCR Combination Assay for Rapid Diagnosis of Swine Erysipelas

We have previously described the creation by Tn916 mutagenesis of avirulent transposition mutants from a highly virulent strain of Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas. In this study, we cloned a 2.2-kb DNA fragment which flanked the Tn916 insertion in an avirulent mutant (strain 33H6) and evaluated the possibility that this region could be used for the specific detection of E. rhusiopathiae. According to the sequences of this region, oligonucleotide primers were designed to amplify a 937-bp fragment of the E. rhusiopathiae chromosome by PCR. The specificity of the PCR was investigated by analyzing 64 strains of Erysipelothrix species and 27 strains of other genera different from Erysipelothrix. A 937-bp DNA fragment could be amplified from all E. rhusiopathiae strains tested, and no amplification was observed by using DNAs from the other species tested. To make a rapid and definite diagnosis of swine erysipelas in slaughterhouses, we developed an enrichment broth cultivation-PCR combination assay, which used a commercially available DNA extraction kit, to identify E. rhusiopathiae in the specimens from swine with arthritis. After samples were enriched in selective broth culture, detection of E. rhusiopathiae was tested by either conventional methods or the PCR. Of 102 samples tested, 15 samples were positive by conventional methods and 12 of the 15 samples were positive by the PCR. The detection limit of the PCR was 10³ CFU per reaction mixture for the PCR-positive samples. These results indicate that this PCR technique could be used as a first-line screening technique for the specific detection of E. rhusiopathiae in specimens.