Familial dementia with Lewy bodies (DLB).

We report a rare familial case of dementia with Lewy bodies (DLB). The patient was a man who died at the age of 51. His parents were first cousins. Among three siblings, two were diagnosed as probable cases of DLB, and one was a possible case, according to the clinical diagnostic criteria of the consortium on DLB. Following the patient's autopsy, he was found to have had DLB without neurofibrillary tangles or senile plaques (pure form of diffuse Lewy body disease). His other siblings have been followed for more than ten years. Although these patients with familial DLB displayed clinical variability, all three siblings showed progressive dementia of early onset and progressive language disorder with paraphasia and difficulty in finding words. Psychotic features were also seen in the three siblings. The patient's sister showed compulsive behavior, and the other two siblings showed symptoms of parkinsonism. Neuropathologically, in addition to the usual neuropathology of DLB, the autopsy findings showed numerous small spheroids in the stratum pyramidale from the subiculum to CA1 of the hippocampus. Significant neuronal loss in CA2-3 of the hippocampus was detected. Axonal flow disturbance may be involved in the hippocampal formations of this incidence of familial DLB.     

Respiratory complications of Ehlers–Danlos syndrome type IV

We describe a case of Ehlers–Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient’s death because of pulmonary hemorrhage. Because this syndrome resulted in the patient’s death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death.     

Evaluation of Intrahepatic Perfusion on Fusion Imaging Using a Combined CT/SPECT System: Influence of Anatomic Variations on Hemodynamic Modification Before Installation of Implantable Port Systems for Hepatic Arterial Infusion Chemotherapy

BACKGROUND: In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. METHODS: Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. RESULTS: Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and 3 hypoperfusion. In 2 of 5 patients with LHA replacement, the distribution was homogeneous. In 1 patient with RHA and LHA replacement, and in 1 patient with LHA replacement and an accessory RHA, we noted hypoperfusion in the RHA territory. All 6 patients with homogeneous distribution were classified as PR or NC on follow-up multidetector CT. Of the 7 patients manifesting hypoperfusion, 3 were classified as PD (43%), 3 as NC (43%), and 1 as PR (14%) on follow-up CT. CONCLUSION: Hemodynamic modification of anatomic hepatic artery variations resulted in hypoperfusion on fusion images. Differences in the intrahepatic perfusion patterns may affect the response to hepatic arterial infusion chemotherapy.     

Clinical Analysis of Anatomical Resection for the Treatment of Hepatocellular Carcinoma Based on the Stratification of Liver Function

Background

This study aimed to clarify the efficacy of anatomical resection (AR) for the treatment of hepatocellular carcinoma (HCC) compared with that of nonanatomical resection (NAR) based on the stratification of liver function (LF).

Methods

The clinical records of 174 patients with a single HCC, 2–5 cm in diameter and without macroscopic vascular invasion, were analyzed. AR was performed in 132 patients and NAR was performed in 42 patients. The indocyanine green retention rate at 15 min (ICGR15) of the 78 patients classified as the good-LF group was 10–20 % and the ICGR15 of the 54 patients classified as the poor-LF group was 20–40 %.

Results

The 5-year overall survival (OS) and disease-free survival rates of the 174 patients were 67.6 and 33.4 %, respectively. Cox proportional hazard analysis identified ICGR15 ≥20 %, liver cirrhosis, α-fetoprotein ≥100 mg/dL, and infiltrating growth as independent prognostic factors. Liver cirrhosis was significantly less frequent in patients who underwent AR than in patients who underwent NAR (52 vs. 79 %, p = 0.002). In the subgroup analysis of the good-LF group, there were no significant differences in 5-year OS after AR and NAR (73.3 vs. 65.2 %, p = 0.857). By contrast, in the subgroup analysis of the poor-LF group, the 5-year OS after AR was significantly worse than after NAR (45.3 vs. 77.4 %, p = 0.044).

Conclusion

In patients with an ICGR15 ≥20 %, we recommend NAR rather than AR for the treatment of a solitary 2–5-cm-diameter HCC and without macroscopic vascular invasion.     

Stimulation of osteoblastic cell differentiation by Notch.

Notch is a transmembrane protein that plays a critical role in the determination of cellular differentiation pathways. Although its importance in the development of mesenchymal tissues has been suggested, its role in skeletal tissues has not been well investigated. Northern blot experiments showed the expression of Notch1 in MC3T3-E1 osteoblastic cells at early differentiation stages. When a Notch1 cytoplasmic domain (Notch-IC [NIC]) delivered by an adenovirus vector was expressed in osteoblastic MC3T3-E1 cells, a significant increase in calcified nodule formation was observed in long-term cultures. Activation of endogenous Notch in MC3T3-E1 by coculturing them with Delta-like-1 (Dll1)-expressing myeloma cells also resulted in a stimulation of calcified nodule formation. Not only affecting nodule formation, Notch activation also had effects on osteoblastic differentiation of multipotent mesenchymal cells. Osteoblastic differentiation of C3H10T1/2 cells induced by bone morphogenetic protein 2 (BMP-2) was significantly stimulated, whereas adipogenic differentiation was suppressed strongly, resulting in a dominant differentiation of osteoblastic cells. NIC expression in primary human bone marrow mesenchymal stem cells (hMSCs) also induced both spontaneous and stimulated osteoblastic cell differentiation. These observations suggest that osteoblastic cell differentiation is regulated positively by Notch and that Notch could be a unique and interesting target molecule for the treatment of osteoporosis.     

The carina is not a landmark for central venous catheter placement in neonates

BACKGROUND: Cardiac tamponade is rare but one of the most serious complications in relation to central venous catheters (CVC). The tip of the CVC should be placed outside the pericardium to avoid tamponade. In adults, the carina is always located above the pericardium; therefore, the carina is a reliable landmark for CVC placement. We examined whether the carina could also be an adequate landmark for CVC placement in neonates. METHODS: The study was conducted using nine fresh neonatal cadavers. The longitudinal distance between the carina and the pericardium as it transverses the superior vena cava (the pericardial reflection: PR) was measured. RESULTS: The median postconceptional age (gestational age in weeks + weeks after delivery) at autopsy was 35 (range: 23-42) weeks. The PR was located at a distance of 4 mm above to 5 mm below the carina. Unlike in adults, the position of the PR varies in relation to the carina in neonates. In seven of the nine subjects, the location of the PR was above the carina. CONCLUSIONS: In neonates, the carina is not always located above the pericardium, as it is in adults; therefore, the carina is not an appropriate landmark for CVC placement.     

Low dose DDT inhibition of hepatocarcinogenesis initiated by diethylnitrosamine in male rats: possible mechanisms

Previously we reported a tendency for reduction of the development of glutathione-S-transferase placental form (GST-P) positive foci, recognized as preneoplastic changes in rat liver, by a low dose of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), which belongs to the same group of hepatic cytochrome P-450 inducers as phenobarbital and is itself a non-genotoxic hepatocarcinogen. In order to clarify the biological significance of this phenomenon, we investigated the reproducibility and changes in other parameters using an initiation-promotion model in which male F344 rats were treated with DDT at doses of 0, 0.005, 0.5, 500 ppm in the diet for 11 or 43 weeks after initiation of hepatocarcinogenesis with N-diethylnitrosamine (DEN). When 500 ppm DDT was applied, the formation of GST-P positive foci and tumor were markedly elevated. In contrast, induction of GST-P positive foci and liver tumors tended to be inhibited at a dose of 0.005 ppm, correlating with protein levels of cytochrome P450 2B1 and 3A2 (CYP2B1 and 3A2) and generation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. mRNA levels for 8-oxoguanine glycosylase 1 (OGG1), an 8-OHdG repair enzyme, connexin 32 (Cx32), a major component of Gap junctions, and hepatic nuclear factor 1alpha (HNF-1alpha), a Cx32 regulator, were inversely correlated with GST-P positive foci and tumor formation. These results indicate that low dose DDT may indeed exhibit inhibitory effects on chemically initiated-rat hepatocarcinogenicity, in contrast to the promotion observed with high doses, and that this is related to changes in metabolizing enzymes, cell communication, and DNA damage and its repair.     

Analysis of patient load data from the 2002 FIFA World Cup Korea/Japan

INTRODUCTION: Past history of mass casualties related to international football games brought the importance of practical planning, preparedness, simulation training, and analysis of potential patient presentations to the forefront of emergency research. METHODS: The Japanese Ministry of Health, Labor, and Welfare established the Health Research Team (HRT-MHLW) for the 2002 FIFA World Cup game (FIFAWC). The HRT-MHLW collected patient data related to the games and analyzed the related factors regarding patient presentations. RESULTS: A total of 1661 patients presented for evaluation and care from all 32 games in Japan. The patient presentation rate per 1000 spectators per game was 1.21 and the transport-to-hospital rate was 0.05. The step-wise regression analysis identified that the patient presentations rate increased where access was difficult. As the number of total spectators increased, the patient presentation rate decreased. (p < 0.0001, r = 0.823, r2 = 0.677). CONCLUSION: In order to develop mass-gathering medical-care plans in accordance with the types and sizes of mass gatherings, it is necessary to collect data and examine risk factors for patient presentations for a variety of events.     

Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II-IVB)

PURPOSE: To discover possible risk factors for local-regional recurrence (LRR) following preoperative radiation therapy and curative surgery for head and neck squamous cell carcinoma (SCC) (stage II-IVB). MATERIALS AND METHODS: Clinical records from 1987 to 1999 of 161 patients with head and neck SCC (oral cavity, 80 patients; larynx, 50; hypopharynx, 19; oropharynx, 12) who underwent preoperative radiation therapy and surgery were retrospectively reviewed. One hundred thirty-two (82%) of the patients had stage III or IV cancer. The median radiation dose was 38 Gy. RESULTS: The 5-year overall survival rate and LRR rate were 58% and 35%, respectively. At multivariate analysis, oral cavity cancer (P =.020), clinical T stage (P =.016), clinical N stage (P =.017), and status of surgical margins (P =.008) emerged as variables that were significantly associated with LRR. The analysis of only those patients with lymph node involvement showed that oral cavity cancer (P =.008), advanced N-stage cancer (P =.045), and long interval between the start of preoperative radiation therapy and surgery (> or =7 weeks) (P =.019) emerged as variables that were significantly associated with LRR. CONCLUSION: Oral cavity cancer, advanced T or N stage of disease, and unsatisfactory margins were risk factors for LRR. A long interval (> or =7 weeks) was a risk factor for LRR in patients with lymph node involvement.