An autopsy case of acute porphyria with a decrease of both uroporphyrinogen I synthetase and ferrochelatase activities

Summary An autopsy case of a 37-year-old woman with acute porphyria is reported. The patient began to complain of severe menstrual pains, and later developed serious peripheral neuropathy and various autonomic nervous symptoms.The autopsy revealed a marked loss and degeneration of axons and myelin sheaths in the peripheral nervous system (PNS), and prominent central chromatolysis of the spinal anterior horn cells. The predominant process of the peripheral neuropathy appeared to be axonal degeneration.Biochemical analysis showed a marked increase of delta-aminolevulinic acid (ALA), porphobilinogen, uroporphyrin, and coproporphyrin in the urine, and an increase of coproporphyrin and protoporphyrin in the stools and blood. In the analysis of the enzymatic activities of the liver and bone narrow, the activity of ALA synthetase (ALA-S) was markedly increased, and the activities of both uroporphyrinogen I synthetase (URO-S) and ferrochelatase were decreased. It was characteristic in this case that the enzymatic abnormalities found in both acute intermittent porphyria (AIP) and variegate porphyria (VP) coexisted.Biochemical analysis of the sciatic nerve showed an increase of ALA-S activity and a decrease of both URO-S and ALA dehydrase activities. This was the first report that indicated the presence of abnormal activities of the heme biosynthetic enzymes in the peripheral nerves of porphyric patients. The possibility was discussed that these enzymatic abnormalities of the heme biosynthesis in the peripheral nerve itself might be strongly related to the pathogenesis of the porphyric neuropathy.     

Factors Associated with the Clinical Impact of Capsule Endoscopy in Patients with Overt Obscure Gastrointestinal Bleeding

Background and Study Aims  

Capsule endoscopy (CE) does not necessarily identify positive findings in patients with overt obscure gastrointestinal bleeding (OGIB). We aimed to identify factors predictive of positive CE findings and those of re-bleeding after negative CE in overt OGIB.     

Exploring the Feasibility of Dose Escalation Positron Emission Tomography–Positive Disease with Intensity-Modulated Radiation Therapy and the Effects on Normal Tissue Structures for Thoracic Malignancies

The pattern of failure is one of the major causes of mortality among thoracic patients. Studies have shown a correlation between local control and dose. Intensity-modulated radiation therapy (IMRT) has resulted in conformal dose distributions while limiting dose to normal tissue. However, thoracic malignancies treated with IMRT to highly conformal doses up to 70 Gy still have been found to fail. Thus, the need for dose escalation through simultaneous integrated boost (SIB) may prove effective in minimizing reoccurrences. For our study, 28 thoracic IMRT plans were reoptimized via dose escalation to the gross tumor volume (GTV) and planning target volume (PTV) of 79.2 Gy and 68.4 Gy, respectively. Reoccurrences in surrounding regions of microscopic disease are rare therefore, dose-escalating regional nodes (outside GTV) were not included. Hence, the need to edit GTV margins was acceptable for our retrospective study. A median dose escalation of approximately 15 Gy (64.8–79.2 Gy) via IMRT using SIB was deemed achievable with minimal percent differences received by critical structures compared with the original treatment plan. The target's mean doses were significantly increased based on p-value analysis, while the normal tissue structures were not significantly changed.     

Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: A pilot study

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200–300 mg/m²/day) and cytosine arabinoside (100 mg/m²/day) by 24 h continuous infusion for 5–7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).     

Relation between self-reported weight cycling history, dieting and bio-behavioral health in Japanese adult males

Background Epidemiological findings suggest that weight fluctuations are associated with unfavorable health outcomes compared with stable weight. However, the interrelationship between the weight cycling history and dieting status in a non-clinical male trial on the risk for bio-behavioral health is unclear. Objective The purpose of this study was to examine the relation between weight cycling history as a result of intentional weight loss and bio-behavioral health in Japanese adult males. Method A cross-sectional study was performed on a group of 146 Japanese working males (47.5±9.3 yr.). Each subject completed a series of self-reported questionnaires in which information about weight cycling history, current dieting practices, life-styles, and social background were assessed. Results of the physical check up were used to assess biological parameters. Self-reported weight cycling was defined as intentionally losing 10% of one's weight and regaining the lost weight. Results Cyclers reported a significantly greater incidence of current dieting and recent weight gain compared with non-cyclers. Taking regular meals, eating breakfast everyday, and not eating snacks between meals every day were significantly less frequent among cyclers compared with non-cyclers after controlling for BMI. The adjusted odds ratio for AST abnormality was 5.46 (95% CI: 1.08–27.67), ALT abnormality was 3.31 (95% CI: 1.24–8.78), and γ-GTP was 3.38 (95% CI: 1.07–10.67) among cyclers, compared with noncyclers. Conclusion These findings suggest that a history of weight cycling in men, regardless of current weight status, is associated with adverse bio-behavioral health. The risk for several liver enzyme abnormalities associated with weight cycling history was substantial, independent of relative body weight and lifestyle factors.     

Central projections of thoracic splanchnic and somatic nerves and the location of sympathetic preganglionic neurons in Xenopus laevis

The central and peripheral organization of thoracic visceral and somatic nervous elements was studied by applying dextran amines to the proximal cut ends of the thoracic splanchnic and somatic nerves in Xenopus laevis. Many labeled dorsal root ganglion cells of visceral afferents, and all somatic afferents, were located in a single ganglion of one spinal segment, and the two types of cells were distributed topographically within the ganglion. The labeled sympathetic preganglionic neurons were located predominantly in the same area of the thoracic spinal gray as in other frogs and in mammals. The labeled visceral afferents projected to Lissauer's tract and the dorsal funiculus. The visceral fibers of the tract ascended to the level of the subcerebellar area, supplying collateral branches to the lateral one-third of the dorsal horn and to the area of brainstem nuclei, including lateral cervical and descending trigeminal nucleus, and descended to the filum terminale. The visceral fibers of the dorsal funiculus were distributed to the dorsal column nucleus and the solitary tract. A similar longitudinal projection was also seen in the somatic afferents. The dual central pathway of thoracic primary afferents in the anuran spinal cord is a property held in common with mammals, but the widespread rostrocaudal projection through Lissauer's tract may be a characteristic of the anuran central nervous system. In frogs, the direct transmission of primary afferent information to an extremely wide area of the central nervous system may be important for prompt assessment of environmental factors and control of body functions.