Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Effect of porcine placental extract on the mild menopausal symptoms of climacteric women.

OBJECTIVES: This study assessed the effects of oral porcine placental extract (PPE) on the mild menopausal symptoms of climacteric women. METHODS: In this 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, 50 climacteric Japanese women were randomized 1 : 1 to oral PPE (300 mg/day) or placebo. Menopausal symptoms were evaluated by using the Simplified Menopausal Index (SMI), as were serum estradiol (E2) and follicle stimulating hormone (FSH) levels. Blood biochemical and cellular and urinary tests were done to evaluate safety aspects of repeated oral administration of PPE. RESULTS: The total SMI score of the PPE group was significantly more improved after 12 weeks than that of the placebo group (p = 0.031). This score and three subscores (vasomotor, psychological, and somatic symptoms) were significantly improved at 8 and/or 12 weeks compared with the initial values in the PPE group (p < 0.05). E2 and FSH levels were not improved in either group. No adverse events were observed. CONCLUSIONS: Oral PPE at 300 mg/day improved the mild menopausal symptoms of climacteric women. Since oral PPE did not improve serum E2 and FSH levels, PPE is thought not to ameliorate hormonal balance itself but to improve subjective feelings of climacteric women.

Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein.

AIM: To investigate whether mouse bone marrow mesenchymal stem cells (BMC) stimulate liver regeneration after partial hepatectomy. METHODS: Isolated BMCs were purified by density gradient centrifugation. We performed a 70% hepatectomy in male BALB/c mice followed by injection of BMCs into the portal vein (PV-BMC group), or the tail vein (IV-BMC group), or of saline into the portal vein (control group). RESULTS: The wet weight of the liver remnant increased significantly in the PV-BMC group at 3 and 5 days after hepatectomy compared with the IV-BMC and control groups. The Ki-67 labeling index revealed that the increase to result from stimulation of DNA synthesis. The constitutive interleukin-6 and hepatocyte growth factor mRNAs in the remnant liver tended to increase in the PV-BMC group at 3 days after hepatectomy. CONCLUSIONS: These results demonstrated that BMC injection into the portal vein enhanced liver growth after partial hepatectomy in mice.

Epidermotropic CD8+ cytotoxic T-cell lymphoma exhibiting a transition from the indolent to the aggressive phase, accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.

A 47-year-old-man presented with rashes on his trunk and limbs, and a diagnosis of parapsoriasis was made. Ten years later, the rashes had progressed gradually to form plaques and tumours. Gene rearrangement studies revealed monoclonality of the T-cell receptor ß-chain (TCR-Jß)1 gene, and results of flow cytometry and immunohistochemical examination confirmed a diagnosis of epidermotropic CD8+ cytotoxic T-cell lymphoma. The clinical course of the disease remained indolent for some time, but about 2 years later, neutrophilic pustules formed on the surface of the skin lesions, and tumours developed in the patient's testes. Using flow cytometry, emergence of CD7+ cells was found. The patient died the following year of respiratory failure due to brain herniation. On postmortem examination, CD8+ tumour cells were found in the brain. This case demonstrates an unusually protracted indolent phase in a patient with cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; its transition into the aggressive phase was accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.

PTH and stem cells.

At least 2 different types of cells, hematopoietic and mesenchymal, are present in the adult bone marrow, in addition to endothelial cells. Hematopoietic and mesenchymal cells are believed to originate from hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC), respectively. The bone marrow stroma, a cellular microenvironment that supports HSC, is composed of non-hematopoietic cells and contains MSC. A unique expansion of the bone marrow stroma, also known as marrow fibrosis, is the hallmark of a variety of disorders including hyperparathyroidism and fibrous dysplasia. PTH is the first bone anabolic agent approved by US Food and Drug Administration for the treatment of osteoporosis. Recent studies have suggested that PTH treatment may affect the number of hematopoietic stem cells in the bone marrow and their mobilization into the bloodstream. In addition, cells with classical features of mesenchymal stem cells/progenitors have been shown to express receptors for PTH, and to increase in number and undergo redistribution in the adult bone marrow upon PTH treatment. In this review, we will summarize the up-to-date knowledge on PTH and its relation to stem cells. We will also discuss the contribution of different cell types to the development of marrow fibrosis and the involvement of PTH signaling in this pathology.

Patency assessment of the internal jugular vein after neck dissection.

Twenty-seven patients with oral malignant tumours, who underwent neck dissection with preservation of the internal jugular vein (IJV), were studied retrospectively to evaluate patency of the IJV. Twenty-three patients underwent ablative surgery of the primary lesion with neck dissection and 4 underwent neck dissection alone. Three patients received simple closure and skin grafting of the primary lesion, and 20 received reconstruction surgery (4 platysma flaps, 3 radial forearm flaps, 3 lateral upper arm flaps, 2 pectoralis major myocutaneous flaps and 8 rectus abdominis myocutaneous flaps). The maximum and minimum diameters of the IJV as measured on computed tomographic (CT) scans were used to assess patency. The cross-sectional area of the IJV and the ratio of its long axis to short axis (L/S ratio) were calculated. The relation between the change in IJV status and the type of flap used for reconstruction was also examined. Occlusion of the IJV was present in 3.7% of the patients, and 'narrowing' was present in 63.6%. The size of the flap significantly correlated with 'narrowing' of the IJV, suggesting that 'narrowing' was caused mainly by compression due to the flap.

Healing of fractures in osteoporotic rat mandible shown by the expression of bone morphogenetic protein-2 and tumour necrosis factor-alpha.

We studied the healing process of mandibular closed fractures in osteoporotic rats using specific antibodies to bone morphogenetic protein-2 (BMP-2) and tumour necrosis factor-alpha (TNF-alpha). We confirmed the osteoporosis in rats after oophorectomy by micro-CT, and then caused unilateral closed fractures in the mandible and monitored the healing process after 7, 14, 21, and 28 days. Data were compared simultaneously with those from a group of rats that had a sham operation. During healing of the fracture in the osteoporotic group there was a prolonged phase of endochondral ossification, with an increased number of osteoclasts (p<0.01). Expressions of BMP-2 and TNFalpha were more pronounced in the osteoporotic group and there was an increase in the number of osteoblasts and TNFalpha(+) cells compared with the normal control (p<0.01). BMP-2 was related to the differentiation of osteoblasts and the higher values of TNFalpha were correlated with the up-regulation of osteoclasts during the prolonged phase of bone turnover. We conclude that the healing of fractures in osteoporotic bone is delayed about a week compared with controls. In the healing of fractures in osteoporotic bone, there were more osteoblasts and osteoclasts but there was a predominance of osteoclasts probably induced by TNFalpha. The prolonged phase of bone turnover with osteoclast predominance in the osteoporotic group is suggestive of the cause of delay in the healing of the fracture.

Application of fuzzy inference to European patients to predict cervical lymph node metastasis in carcinoma of the tongue.

In head and neck cancers, the presence of cervical lymph node metastasis is an important determinant of outcome. Many attempts have been made to predict cervical lymph node metastasis, but the accuracy of currently available techniques remains inadequate. We used fuzzy inference to predict cervical lymph node metastasis retrospectively in 75 patients with squamous cell carcinoma of the tongue and prospectively in 23 patients. Our model was based on three variables: tumor size, keratinization, and mode of invasion. The accuracy of fuzzy inference for the prediction of cervical lymph node metastasis in the 75 patients studied retrospectively was 86.7%, the sensitivity was 70.8%, and the specificity was 94.1%. In the 23 patients studied prospectively, the accuracy was 91.3%, the sensitivity was 50.0%, and the specificity was 95.2%. The accuracy obtained in this European series of patients was similar to that previously obtained in Japanese patients. We conclude that fuzzy inference may be a useful method for predicting cervical lymph node metastasis. Its high specificity is likely to reduce the number of unnecessary neck dissections. However, the current level sensitivity is inadequate for routine clinical use. Therefore, other predictors of lymph node metastasis should be identified to refine the current model.

Comparison of the healing process in plated and non-plated fractures of the mandible in rats.

We compared the healing process of plated and non-plated fractures. The mandibles of 72 male Wistar rats were fractured and more either plated or not plated (n = 36 in each group). The healing process of the two conditions was studied histologically and immunohistochemically using a specific antibody to bone morphogenetic protein-2 (BMP-2). The results showed that the healing process in the plated group was delayed by one week compared with the non-plated group. Trauma to the surrounding soft tissues affected the healing process. BMP-2 was expressed at all stages in both groups. We conclude that the healing process is disturbed by the fixing of a plate; that periosteum is one of the main sources of osteogenic cells; and that BMP-2 is an important regulator of morphogenesis.

Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor.

Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. Especially, nifedipine, among many calcium antagonists, was shown to improve endothelial dysfunction in patients with hypertension. However, no report has determined whether the improvement of endothelial dysfunction by nifedipine is due to direct effects or indirect effects such as its hypotensive effect. Thus, in this study, we evaluated the direct effects of nifedipine on smoking-induced endothelial dysfunction, since cigarette smoking itself is a major factor in damage of endothelial cells, as well as hypertension. We examined whether nifedipine improves endothelial function in 10 normotensive smokers without any risk factors for atherosclerosis. The subjects were treated with 20 mg nifedipine monotherapy (n = 10) or placebo (n = 10) for 4 weeks. Nifedipine did not affect blood pressure and heart rate of normotensive smokers. We measured forearm blood flow (FBF) by strain-gauge plethysmography after 2 and 4 weeks of treatment. Changes in vasodilator response to reactive hyperaemia were significantly improved in nifedipine-treated subjects (P < 0.05), while there was no significant change in FBP response in control subjects. Response to nitroglycerin was not changed in either group. Moreover, to evaluate the mechanisms of the direct effects of nifedipine on the endothelium, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an antiapoptotic action on endothelial cells. Interestingly, serum HGF concentration in smokers treated with nifedipine was significantly elevated both at 2 and 4 weeks (P < 0.05). Overall, these results demonstrated direct effects of nifedipine in the improvement of endothelial dysfunction in normotensive smokers. The increase in serum HGF concentration by nifedipine might contribute to the improvement of endothelial dysfunction.

Endoscopic removal of a dental implant displaced into the maxillary sinus: technical note.

Minimal invasive endoscopic surgery has been developed for various indications in the cranio-maxillofacial area. In this article, a technique for endoscopic removal of a dental implant displaced into the maxillary sinus is presented. Access to the implant was achieved transorally via the canine fossa. The implant was captured and removed using a urological retrieval basket through the endoscopic working channel port. The endoscopic surgical approach described was reliable and minimally invasive for removing dental materials displaced into the maxillary sinus.

Characterization of dental epithelial progenitor cells derived from cervical-loop epithelium in a rat lower incisor.

Dental epithelial progenitor cells differentiate into various cell types during development of tooth germs. To study this mechanism, we produced immortalized dental epithelial progenitor cells derived from the cervical-loop epithelium of a rat lower incisor. The expression patterns of cytokeratin 14, nerve growth factor receptor p75, amelogenin, Notch2, and alkaline phosphatase were examined by immunohistochemistry in both lower and higher cell densities. The patterns of each were compared in the dental epithelium of rat lower incisors. The results demonstrated that these cells could produce ameloblast lineage cells, stratum intermedium cells, stellate reticulum, and outer enamel epithelium. Furthermore, fibroblast growth factor 10 stimulated proliferation of dental progenitor cells and subsequently increased the number of cells expressing alkaline phosphatase. These results suggest that fibroblast growth factor 10 plays a role in coupling mitogenesis of the cervical-loop cells and the production of stratum intermedium cells in rat incisors.

Midkine induced growth of ameloblastoma through MAPK and Akt pathways.

Midkine (MK) is expressed during tooth development and, since ameloblastoma is thought to be arisen from the epithelium of the odontogenic apparatus or its remnant tissues, the effect of MK in ameloblastoma cell growth should be examined. The expression and function of MK were examined using 37 ameloblastoma tissues and AM-1 cells, an HPV-16DNA transfected ameloblastoma cell line. We found that MK was immunohistochemically expressed in 70% of ameloblastoma cases and AM-1 cells. By stimulation with 100 ng/ml MK, the growth of AM-1 cells was accelerated two fold by the 9th day. MK could induce phosphorylation of p44/42 MAPK (Thr202/Tyr204) and Akt (Ser473 and Thr308), and by pretreatment of PD98059, MEK1 inhibitor, or LY294002, PI3K inhibitor, MK-stimulated-phosphorylation of MAPK and Akt and MK-stimulated growth of AM-1 cells were inhibited. These results suggested that MK induced growth of ameloblastoma is through the MAPK and Akt pathways.

Mast cell chymase expression in Helicobacter pylori-associated gastritis.

AIMS: To study the role of mast cell chymase in the inflammatory processes of human chronic gastritis. Experimental studies have shown that mast cell chymase stimulates inflammatory cell accumulation, and contributes to angiotensin II formation. METHODS AND RESULTS: Tissue sections from human stomachs with Helicobacter pylori-associated gastritis (surgery/autopsy n = 20; biopsy n = 16) and normal stomachs (n = 10) were studied using immunohistochemical single and double labelling techniques. Monoclonal antibodies used were directed against mast cell chymase, tryptase, neutrophils (CD66b, elastase, and myeloperoxidase), macrophages, T-lymphocytes, and interleukin (IL)-4. The expression of angiotensin-converting enzyme and angiotensin II type 1 receptor was investigated using immunohistochemical analysis and the reverse transcription-polymerase chain reaction. The number of chymase-positive mast cells was significantly higher (P < 0.0001) in H. pylori-associated gastritis than in normal stomachs. Increased expression of chymase in inflamed mucosa was closely related to an increase in the accumulation of neutrophils, macrophages, T-lymphocytes, and IL-4-positive cells. The expression of angiotensin-converting enzyme and angiotensin II type 1 receptor was not altered in gastritis specimens. CONCLUSIONS: These observations suggest that mast cell chymase may be an important mediator in the inflammatory processes of human H. pylori-associated gastritis.

TGF-beta 3 decreases type I collagen and scarring after labioplasty.

Cleft lip is a common congenital malformation, and labioplasty performed on infants to repair such defects often results in severe scar formation. Since TGF-beta 3 has been implicated in wound healing, we therefore hypothesized that TGF-beta 3 functions to reduce scarring after cleft lip repair. In this investigation, we demonstrated that exogenous TGF-beta 3 reduced scar formation in an incised and sutured mouse lip in vivo. During labioplasty, endogenous TGF-beta 3 expression was also elevated. In vitro experiments showed that exogenous TGF-beta 3 reduced type I collagen accumulation. Furthermore, TGF-beta 3 inhibited alpha-smooth-muscle actin expression, a marker for myofibroblasts. In tandem, TGF-beta 3 induced the expression and activity of MMP-9. Analysis of our data suggests that TGF-beta 3 is normally secreted following labioplastic wound healing. An elevated level of TGF-beta 3 reduces type I collagen deposition by restricting myofibroblast differentiation and thereby collagen synthesis, and by promoting collagen degradation by MMP-9. In combination, these events lead to TGF-beta 3-mediated reduced scar formation.

Platelet-derived growth factor and bone morphogenetic protein in the healing of mandibular fractures in rats.

We studied the effects of platelet-derived growth factor-B (PDGF-B) and bone morphogenetic protein-2 (BMP-2) during the healing of mandibular closed fractures in rats by immunohistochemical methods. Unilateral closed fractures were created in the mandibles of thirty 12-week-old rats. BMP-2 was expressed during all stages of healing, but PDGF-B was expressed mainly in the early and middle stages, and not in the later stage of the healing process. We conclude that PDGF-B was associated with the proliferation and migration of primitive mesenchymal cells. BMP-2 was related to the differentiation of mesenchymal cells into osteoblasts and chondroblasts. PDGF-B and BMP-2 both have distinct regulatory effects on the healing of fractures.

TGF-beta-3 promotes scarless repair of cleft lip in mouse fetuses.

TGF-beta3 mediates epithelial-mesenchymal transformation during normal fusion of lip and palate, but how TGF-beta3 functions during cleft lip repair remains unexplored. We hypothesize that TGF-beta3 promotes fetal cleft lip repair and fusion by increasing the availability of mesenchymal cells. In this investigation, we demonstrated that cleft lips in mouse fetuses were repaired by fetal surgery, producing scarless fusion. At the site of the operation, we first observed an infusion of platelets expressing TGF-beta3, followed by increased expression of cyclin D1 and tenascin-C, and coupled with increased mesenchymal cell proliferation. In an ex vivo serumless culture system, cleft lip explants fused in the presence of exogenous TGF-beta3. Cultured lips also showed up-regulation in cyclin D1 and tenascin-C expression. These findings suggest that microsurgical repair of cleft lip in the fetus that produced scarless fusion is mediated by TGF-beta3 regulation of mesenchymal cell proliferation and migration at the site of repair.

The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.