Immunocytochemical localization of kisspeptin neurons in the rat forebrain with special reference to sexual dimorphism and interaction with GnRH neurons

Kisspeptin/metastin has been implicated as a critical regulator in luteinizing hormone (LH) secretion and the reproductive system mediating the effect of estrogen on GnRH neurons. In the present study we examined the sex differences in the effects of estrogen on Kiss1/kisspeptin expression in the forebrain by using gonadectomized rats to assess the interaction of kisspeptin and GnRH neurons. Kiss1/kisspeptin cell bodies were abundant in the rostral periventricular area of the third ventricle (RV3P) and the arcuate nucleus (ARC). A few cell bodies were also observed in other portions of the forebrain, i.e. the bed nucleus of the stria terminalis (BST), the paraventricular hypothalamic nucleus (PaAP), the ventromedial hypothalamic nucleus (VMH), and the medial amygdaloid nucleus (MeA). Kisspeptin-immunoreactive fibers were found mainly in the median eminence (ME), the ARC, and the RV3P, but were scarce in the preoptic area (POA), where GnRH neurons are localized. We also found that estrogen triggers expression of the Kiss1 gene and peptide within all the regions except the ARC, and that the effects in the RV3P, BST, PaAP, and VMH are greater in estrogen treated ovariectomized female rat. It is noteworthy that kisspeptin and GnRH neurons were densely associated in the ME but were rarely in contact in the POA. Thus, our results suggest that kisspeptin-positive neurons, except for the ones in the ARC, are related not only to estrogen-positive feedback, but also sex dimorphism, and that kisspeptin regulates GnRH release in the ME rather than the POA.     

Communicating arcade between the right and left hepatic arteries: evaluation with CT and angiography during temporary balloon occlusion of the right or left hepatic artery

PURPOSE: To evaluate prospectively the relationship between the arterial collateral system at the hepatic hilum and the blood supply to the hilar bile duct by using computed tomography (CT) and angiography during temporary balloon occlusion of the right or left hepatic artery. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. The study included 13 patients with no lesions at the hepatic hilum (eight men and five women; age range, 41-78 years; mean, 65.8 years). After serial angiographic studies were performed for preoperative evaluation or transcatheter arterial chemoembolization, a 5.5-F catheter with an occlusion balloon was positioned in the right or left hepatic artery. Eleven patients underwent angiography of the left hepatic artery with temporary occlusion of the right hepatic artery, and two patients underwent angiography of the right hepatic artery with temporary occlusion of the left hepatic artery. In addition, 11 patients underwent single-level dynamic CT during hepatic arteriography (CTHA) with temporary occlusion of the right or left hepatic artery. The images from angiography and CTHA were interpreted by two authors who assessed the existence of the arterial communication and its branching points, location, and relationship to the hilar bile duct and caudate lobe. RESULTS: During temporary occlusion of the right or left hepatic artery, the communicating arcade (CA) between the right and left hepatic arteries was immediately evident in all patients. On the left side, the CA originated from the segment IV artery in eight patients (62%) and from the left hepatic artery in five (38%). On the right side, the CA originated from the right anterior hepatic artery in six patients (46%), the right hepatic artery in two (15%), and both arteries in five (38%). The CA was extrahepatically located close to the hilar bile duct and forked into a few branches to the caudate lobe. CONCLUSION: The CA may play an important role not only in the interlobar arterial collateral system but also in the blood supplies to the caudate lobe and hilar bile duct.     

Anterior fissure of the right liver--the third door of the liver

Background/Purpose Although the anterior segment of the liver has been divided into segments 8 and 5, we have, during surgical or interventional procedures, occasionally encountered patients in whom the right anterior portal vein does not bifurcate into the superior and inferior branches. Thus, the in vivo anatomy of the right liver was reevaluated to clarify the segmental anatomy.Methods We evaluated the hepatic venous and portal ramification patterns, using three-dimensional images reconstructed from computed tomography. In addition, liver volumetry was performed.Results All branches arising from the anterior trunk were divided into two groups: the right ventral portal branches (RVP) and the right dorsal portal branches (RDP), and the anterior fissure vein crossed between the RVP and RDP. The ventral and dorsal regions of the anterior segment were approximately equal from a volumetric point of view.Conclusions The anterior segment seems to be divided into the ventral and dorsal segments by the anterior fissure, and we propose a reclassification of the right liver that divides the right liver into three segments. Dissection of the parenchyma along the anterior fissure makes the third door of the liver open, resulting in the exposing of all Glissonian pedicles of the right liver. The introduction of our segmental anatomy and surgical procedure will allow more systematic and limited liver resections.     

A case of ANCA-associated vasculitis with diffuse alveolar hemorrhage successfully treated by plasmapheresis]

A 65-year-old man was admitted due to rapidly progressing dyspnea experienced over a 3-day period. Chest radiography and computed tomography conducted upon admission showed diffuse bilateral interstitial infiltrate. Bronchoalveolar lavage fluid contained blood and siderophores, which suggested pulmonary alveolar hemorrhage. Laboratory data showed that the serum MPO-ANCA level was elevated, and so ANCA-associated pulmonary hemorrhage was diagnosed. Although aggressive immunosuppressive agents were administered, including steroids and cyclophosphamides, the patient's condition worsened. Plasmapheresis using fresh frozen plasma was performed on day 5, after which his symptoms improved dramatically. Plasmapheresis was done 6 times, and the pulmonary lesions resolved. The patient was discharged 6 months later. This case report suggests that plasmapheresis may be an effective treatment for ANCA-associated vasculitis with diffuse alveolar hemorrhage that is resistant to aggressive immunosuppressive therapy.     

Analysis of <Emphasis Type="Italic">PALB2</Emphasis> mutations in 155 Japanese patients with breast and/or ovarian cancer

Background

PALB2 (Partner and Localizer of BRCA2) was identified as a moderate-risk gene in breast and pancreatic cancers. Recently, it was reported that PALB2 carriers have a high risk of developing breast cancer, with the cumulative risk of 34 % by the age of 70.

Patients and methods

Peripheral blood samples from 155 patients at risk for hereditary breast and/or ovarian cancer were tested for BRCA1/2 and PALB2 by targeted sequencing using a next-generation sequencer. Of these 155, 146 met NCCN criteria and the remaining 9 did not.

Results

BRCA1/2 analysis was performed on 155 patients, for whom the results were reported previously (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). Eleven patients were identified to have deleterious BRCA mutations (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). However, none of the 155 patients were found to have deleterious PALB2 germline mutations. Missense mutations [variants of uncertain significance (VUS)] of PALB2 were found in 12 cases. In silico analyses by SIFT (Sorting Intolerant Form Tolerant) and PolyPhen2 (Polymorphism Phenotyping version 2) indicated that 2 of 12 VUS were deleterious and probably damaging.

Conclusions

This is the first report on PALB2 mutations in Japan, revealing two missense mutations as “deleterious and probably damaging” by in silico analyses, but no PALB2 premature truncation mutations were identified. The sample size is relatively small and a larger cohort study is needed in Japan.

     

Effects of bronchoscopic lung volume reduction using transbronchial infusion of autologous blood and thrombin in patients with severe chronic obstructive pulmonary disease

Background

Existing medical treatments have limitations in the management of very severe chronic obstructive pulmonary disease (COPD).

Methods

We performed bronchoscopic lung volume reduction (BLVR) using transbronchial infusion of autologous blood and thrombin (BLVR with blood) in three patients with very severe COPD whose dyspnea could not be relieved by maximum medical management. Two patients underwent BLVR with blood in the left and right lungs at intervals of a half-year or a year, and one patient underwent this procedure in only the right lung. We assessed the changes in pulmonary function, exercise capacity and quality of life before and after BLVR with blood in a total of five procedures.

Results

The subjects were 58- to 74-year-old males. Their forced expiratory volume in one second (FEV₁) percent predicted ranged from 14.8% to 23.4%. BLVR with blood achieved significant improvements as follows (values before → after the procedure, mean ± standard deviation): FEV₁ 0.45r the L → 0.76r the L (P=0.004), inspiratory capacity 1.50cityo L → 2.05±.05c L (P=0.015), 3-minute walk test 46.8nuteo m → 89.6±34.5 m (P=0.004). Lung function peaked several months after BLVR with blood and returned to nearly the baseline level in 6 months, but exercise capacity was better than that at baseline for at least 12 months. St. George’s Respiratory Questionnaire (SGRQ), measured in two patients before and 12 months after the procedure, showed remarkable improvements (−15.6 and −11.9 units).

Conclusions

BLVR with blood is an effective palliative treatment for very severe COPD.     

Brain abscess induced by Bacillus licheniformis complications in acute myeloid leukemia (AML)

A 64-year-old woman with acute myeloid leukemia, headache, vomiting, and fever exceeding 38.5 degrees C on day 15 during severe neutropenia while undergoing second consolidation chemotherapy presented the next day, with an altered mental state. A space-occupying lesion with ring enhancement was detected in her right frontal lobe on CT, indicting a brain abscess. Treatment was started with 2g/day of meropenem and 2 g/day of vancomycin. Surgical drainage was conducted on day 22 after recovery of her neutrophil and platelet counts. Culture of aspirated pus showed Gram-positive rods subsequently identified as Bacillus licheniformis. Meropenem was administered for 87 days and vancomycin for 44 days. The patient's general condition improved without neurological complications, and her enhanced brain lesion disappeared on day 185. B. licheniformis is often encountered in diagnostic laboratory culture and usually dismissed as a contaminant, but must be considered as a causative agents for brain abscesses in immunocompromised hosts.     

A case report of a patient with advanced rectal cancer who was administered chemotherapy in collaboration with a clinical pathway and visiting nursing care

Recently, chemotherapy for the treatment of colorectal cancer was widely administered in Japan. Many various ideas were necessary to perform safe and efficient chemotherapy at our hospital. We experienced that even a patient with intellectual disability could have chemotherapy carry out smoothly in collaboration with a clinical pathway and visiting nursing care. The patient was a 63-year-old man who underwent low anterior resection of the rectum for advanced rectal cancer on April 2004. Multiple liver metastases had appeared in November 2004. Chemotherapy was administered because of the liver metastases. However, it was difficult to manage the side effect of the chemotherapy and we could not get cooperation from his family. A visiting nursing care was employed in cooperation with outpatient nursing for managing of the side effect. IFL regimen was carried out using a clinical pathway. The response became PD after 5 courses of an IFL regimen. The regimen was changed to FOLFOX4 on April 2005. No adverse events were seen beyond grade 2 during 10 courses of FOLFOX4 regimen.