Perioperative management of severe anorexia nervosa.

As the prevalence of anorexia nervosa (AN) increased, surgery in severe AN patients also increased in the 2000s. We experienced a surgical case of a patient with severe AN, showing an extremely low BMI of 8.6 kg m(-2). We investigated the problems associated with this case and propose criteria to manage severe AN. We endeavour to report on the perioperative management of rare and severe symptoms and surgical indications of severely malnourished patients. All published reports were identified through comprehensive searches using PubMed, BioMedLib, and the Japan Medical Abstracts Society with the following terms and keywords: 'anorexia nervosa', 'eating disorder', 'hypoglycaemia', 'leucocytopaenia', 'gelatinous bone marrow', 'surgery', and 'operation'. In cases of AN with a BMI under 13 kg m(-2), marked hypoglycaemia, leucocytopaenia <3.0×10(9) litre(-1), or both, potentially fatal complications frequently occur. Accordingly, patients need strict nutritional support to avoid re-feeding syndrome until surgery. During the course of anaesthesia, careless loading of glucose or catecholamine may lead to disturbance of electrolytes or fatal arrhythmia. Intensive care and early feeding as soon as possible after surgery are important to prevent surgical site infection. Although not many perioperative cases of AN have been reported, clinicians must be aware of the danger and the causes of mortality in critical cases. Thus, the decision to undertake surgery must be taken carefully and close perioperative coordination among physicians, surgeons, psychiatrists, anaesthesiologists, and intensivists is essential.

Analysis of serum chemokine levels in patients with HIV-associated eosinophilic folliculitis.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection exhibit various skin diseases. HIV-associated eosinophilic folliculitis (EF) and pruritic papular eruption (PPE) are frequently seen. OBJECTIVE: To understand the mechanisms underlying HIV-associated EF and PPE. METHODS: In order to know frequencies of EF and PPE among patients with HIV infection, we first collected HIV(+) patients who visited dermatology clinic in National Center for Global Health and Medicine during February 2007. We next collected 25 serum samples from HIV(+) patients with skin diseases from May 2008 to May 2010. Eight of 25 patients had EF (EF group), four had PPE (PPE group) and others had non-itchy skin problems such as condyloma acuminatum (no itch group). RESULTS: We first confirmed high frequencies of EF (10.7%) and PPE (5.3%) among 75 HIV(+) patients who visited our clinic during one month. We then measured serum levels of CCL11, CCL17, CCL26 and CCL27. Serum CCL17 levels in EF were significantly higher than those of PPE and no itch group. Serum CCL26 and CCL27 levels in EF were higher than those of no itch group. The number of CD4(+) cells in EF was significantly lower than that in no itch group. CONCLUSION: High serum levels of CCL17, CCL26 and CCL27, and low CD4(+) cell counts may account for the development of HIV-associated EF.

Diagnostic accuracy of 18F-2-deoxy-fluoro-D-glucose positron emission tomography for pN1 lymph nodes in patients with lung cancer.

BACKGROUND: Nodal status has been reported to be one of the most important factors affecting survival in patients with lung cancer. For determining treatment strategy, accurate evaluation of nodal status is expected. PURPOSE: To evaluate the accuracy of (18)F-2-deoxy-fluoro-D-glucose (FDG) positron emission tomography (PET) for diagnosing nodal status in lung cancer patients with pathologically proven N1 (pN1) lymph node metastases, in comparison with that of computed tomography (CT). MATERIAL AND METHODS: Nineteen pN1 patients with primary lung cancer undergoing preoperative CT and FDG-PET were investigated. The diagnosis was confirmed by surgery in all patients. Lymph nodes were considered to be positive when uptake higher than the surrounding mediastinum level was visually observed. Radiological and pathological correlation was investigated, and the association between FDG uptake and the size of metastatic nodes was evaluated. RESULTS: Of the 19 pN1 patients, nodal stage determined by FDG-PET was cN0 in eight, cN1 in four, cN2 in six, and cN3 in one. Thus, FDG-PET provided correct N-staging in 21%, under-staging in 42%, and over-staging in 37%. FDG-PET could not depict pN1 lymph node in six (32%) of 19 patients. In two patients (11%), mild symmetrical hilar and mediastinal accumulation was found and considered as benign physiological uptake. In six patients (32%), the ipsilateral mediastinal uptake was depicted and diagnosed as cN2. One patient was diagnosed as cN3 because of FDG accumulation at the supraclavicular fossa. On CT, nodal staging was cN0 in nine, cN1 in six, and cN2 in four. CT staging was therefore correct in 32%, underestimated in 47%, and overestimated in 21%. CONCLUSION: The diagnostic accuracy of FDG-PET (21%) was low and similar to that of CT (32%); under- and over-diagnosis were found in similar proportions. The limitation of FDG-PET should be recognized when nodal staging might alter the therapeutic strategy in patients with primary lung cancer.

Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma: a retrospective survey of 112 adult patients in Japan.

We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12-10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08-20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090-0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.

Treatment of supracondylar fracture of the humerus in children by skeletal traction in a brace.

In 1980, we developed a specially designed brace for treating supracondylar fractures of the humerus in children, along with an easy and safe technique of reduction by skeletal traction. This method, which takes into consideration only the medial tilting and anterior angulation of the distal fragment, achieves complete reduction, ignoring any lateral, posterior and minor rotational displacements of the fragment. Skeletal traction is applied through a screw inserted into the olecranon and the angulation at the fracture site is reduced regardless of the anatomical position without manipulation. We treated 193 children with displaced supracondylar fractures of the humerus using this method between 1980 and 2001. Only four children (2%) developed cubitus varus. The majority obtained an excellent range of movement at the elbow; one had a 25 degree limitation of flexion. This technique is an effective and easy method of treating supracondylar fractures of the humerus in children.

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Reconstruction of a scalp and skull defect with free latissimus dorsi myocutaneous flap following dermatofibrosarcoma protuberans.

A 53-year-old male underwent more than 10 surgical treatments over 14 years, including a simple excision and local flap transfer, after recurrences of dermatofibrosarcoma protuberans of the head. Clinical results indicated that simple excision of dermatofibrosarcoma protuberans should not be performed as initial treatment. Instead, free flap transplantation, which permits a wide excision and complete reconstruction, should be the first treatment option.

Rotatory subluxation of the scaphoid in Kienböck's disease is not a cause of scapholunate advanced collapse (SLAC) in the wrist.

We have examined whether the rotatory subluxation of the scaphoid which is seen in patients with advanced Kienböck's disease is associated with scapholunate advanced collapse (SLAC) wrist. We studied 16 patients (11 men, 5 women) who had stage-IV Kienböck's disease with chronic subluxation of the scaphoid. All had received conservative treatment. The mean period of affection with Kienböck's disease was 30 years (14 to 49). No wrist had SLAC. In eight patients, 24 years or more after the onset of the disease, the articular surface of the radius had been remodelled by the subluxed scaphoid with maintenance of the joint space. The wrists of six patients were considered to be excellent, nine good, and one fair according to the clinical criteria of Dornan. Our findings have shown that rotatory subluxation of the scaphoid in Kienböck's disease is not a cause of SLAC wrist and therefore that scaphotrapeziotrapezoid arthrodesis is not required for the management of these patients.

Anti-U5 snRNP antibody as a possible serological marker for scleroderma-polymyositis overlap.

OBJECTIVE: To determine the prevalence of the anti-U5 small nuclear ribonucleoprotein (snRNP) antibody in patients with systemic sclerosis. METHODS: Sera from 281 patients with systemic sclerosis, including 10 patients with overlapping polymyositis, were assayed using RNA immunoprecipitation and protein immunoprecipitation. RESULTS: Only one serum sample showed precipitation of U5 snRNA with scarce precipitation of U2, U1, U4 and U6 snRNAs. In addition, the serum precipitated a 200 kDa protein. The serum was from a 35-yr-old Japanese male patient with overlapping systemic sclerosis and polymyositis accompanied by large-cell lung carcinoma. The clinical appearance was similar to that of a case reported previously. CONCLUSION: The presence of the anti-U5 snRNP antibody in serum may be specific for scleroderma-polymyositis overlap syndrome.

Kienböck's disease in systemic lupus erythematosus.

We report two cases of Kienböck's disease associated with systemic lupus erythematosus SLE. The characteristics of these cases associated with SLE differed from those previously reported for Kienböck's disease. Corticosteroid may be a cause of Kienböck's disease in SLE.

Clinicopathological significance of fragile histidine triad transcription protein expression in breast carcinoma.

The fragile histidine triad (Fhit) gene, which is frequently lost in many cancers, was identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. Loss of Fhit expression is an important step in tumor progression from premalignancy, to in situ, to invasive breast carcinoma. To determine whether the absence of Fhit protein correlates with other established pathological-clinical parameters or prognosis, we assessed Fhit expression using immunohistochemistry in 166 invasive breast carcinomas. Lost or significantly decreased Fhit protein expression was identified in 70 cases (42.2%). Fhit expression was inversely correlated with histological grade (P < 0.0001), negative estrogen receptor status (P = 0.0016), p53 overexpression (P = 0.0040), and tumor proliferation activity (P = 0.0006). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that reduced expression of Fhit was associated with a poor outcome (P = 0.0086, by log-rank test). Multivariate analysis using the stepwise Cox proportional hazard model showed that lymph node metastasis was related to poor survival rates; in addition, patients with loss of Fhit expression still tended to have poor survival (P = 0.0563). Therefore, loss of Fhit expression is associated with higher malignant phenotypes and appears to be a prognostic factor in breast carcinoma.

The use of sintered bone in spinal surgery.

The sintered bovine bone True Bone Ceramics (TBC) is one of the biomaterials based on calcium phosphate, an organized crystal of bone mineral and a biomaterial possessing a natural trabecular structure. We examined whether the sintered bovine bone can integrate with recipient bone and adjust to the strength of recipient bone for anterior spinal fusion in an animal model. Based on radiographic evaluation, manual palpation, biomechanical testing, and histological examination, spinal fusion with TBC resulted in a composition and structure similar to that of autograft (and to no implantation). TBC, with its moderate strength, tended to adjust to the bone stiffness of the host bone in the respective specimens as new bone growth developed. Our observations warrant further clinical investigation of the use of sintered bone as an effective spinal arthrodesis, especially in patients who have fragile vertebrae, as in osteoporosis.

Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats.

Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation.

Pamidronate-induced remission of pain associated with hypertrophic pulmonary osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic breast carcinoma.

We describe an extremely rare case of a woman with pulmonary metastatic disease from breast cancer, who presented with features of hypertrophic pulmonary osteoarthropathy (HPOA). Pain associated with HPOA may be extremely disabling and resistant to treatment. Treatment with pamidronate, an inhibitor of osteoclastic bone resorption, given every 2 weeks by i.v. drip infusion, led to rapid disappearance of uncontrolled pain caused by HPOA.

Successful non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) for Waldenström's macroglobulinemia with severe pancytopenia.

We report a 62-year-old male who underwent non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) because of his life-threatening severe pancytopenia due to refractory Waldenström's macroglobulinemia. This therapy was performed safely and he made a marked recovery from his cytopenia that had not been improved with any other therapy. Bone marrow aspirates showed post-transplant mixed chimerism during engraftment, and became completely donor-derived after a series of GVHD symptoms, without subsequent donor lymphocyte infusion. Our results suggest that non-myeloablative allogeneic PBSCT could be a good alternative for patients suffering from multi-drug resistant Waldenström's macroglobulinemia.

A mathematical model of axillary lymph node involvement considering lymph node size in patients with breast cancer.

BACKGROUND: Surgical sampling for assessing axillary status has not been considered as a well defined surgical procedure. We have reported that MRI is a good instrument for assessing lymph node size and identifying lymph node position. We also developed a mathematical model that takes into consideration the size of axillary lymph nodes, and retrospectively determined the number and size of the axillary lymph nodes that need to be sampled from level I-II to achieve a greater than 90% probability of metastasis detection after surgical sampling, with the future aim of using MR-axillography to assess lymph node size. METHODS: One thousand nine hundred and thirty four lymph nodes from 102 level I-II dissections performed on T1 and T2 breast cancer patients with nodal metastases were examined histologically and the greatest long-axis dimension on histologic slides was measured. RESULTS: This model permitted determination of the cutoff level necessary for an expected probability of detection of metastasis of over 90%. The cutoff level, regardless of tumor size, is a maximum of 6 nodes removed from level I-II in which the greatest long-axis measurement is greater than or equal to 6 mm. The cutoff level in patients with macrometastatic nodes is a maximum of 3 or 4 nodes in which the long-axis dimensions are greater than or equal to 9 or 7 mm, respectively, removed from level I-II. CONCLUSIONS: This model showed that surgical sampling on the basis of lymph node size might have good potential to detect lymph nodes metastases.

Ulnar deviation after volar subluxation of the proximal interphalangeal joint.

A rare case of irreducible and progressive ulnar deviation after volar subluxation of the proximal interphalangeal joint is presented. An immobilized proximal interphalangeal joint with remaining volar subluxation after improper reduction showed ulnar deviation at 3 weeks after injury. During surgery, the radial collateral ligament was found to be ruptured at its origin, with formation of concomitant scar tissues. There were no apparent lesions at the central slip, lateral band, and volar plate. Interposition of the ruptured ligament and infiltration of the surrounding scar tissues into the proximal interphalangeal joint were identified. Surgical incision of the capsule along the dorsal margin of the radial collateral ligament readily produced successful reduction. The irreducible and progressive ulnar deviation of the proximal interphalangeal joint seemed to result from gradual infiltration of the scar tissues, subsequent to remaining volar subluxation because of interposition of the ruptured collateral ligament.

Quercetin inhibits Shc- and phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells.

Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in various cardiovascular diseases. Ang II-induced cellular events have been implicated, in part, in the activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that daily intake of bioflavonoids belonging to polyphenols reduces the incidence of ischemic heart diseases (known as "French paradox"), the precise mechanisms of efficacy have not been elucidated. Thus, we hypothesized that bioflavonoids may affect Ang II-induced MAP kinase activation in cultured rat aortic smooth muscle cells (RASMC). Our findings showed that Ang II stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 in RASMC. Ang II-induced JNK activation was inhibited by 3,3',4',5,7-pentahydroxyflavone (quercetin), a major bioflavonoid in foods of plant origin, whereas ERK1/2 and p38 activation by Ang II were not affected by quercetin. Ang II caused a rapid tyrosine phosphorylation of Src homology and collagen (Shc), which was inhibited by quercetin. Quercetin also inhibited Ang II-induced Shc.p85 association and subsequent activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in RASMC. Furthermore, LY294002, a PI3-K inhibitor and a quercetin derivative, inhibited Ang II-induced JNK activation as well as Akt phosphorylation. Finally, Ang II-induced [(3)H]leucine incorporation was abolished by both quercetin and LY294002. These findings suggest that the preventing effect of quercetin on Ang II-induced VSMC hypertrophy are attributable, in part, to its inhibitory effect on Shc- and PI3-K-dependent JNK activation in VSMC. Thus, inhibition of JNK by quercetin may imply its usefulness for the treatment of cardiovascular diseases relevant to VSMC growth.

Hypermethylation does not account for the frequent loss of the retinoic acid receptor beta2 in breast carcinoma.

Hypermethylation of the retinoic acid receptor (RAR) beta2 has been detected in breast cancer cell lines and is known to repress the level of RAR beta2 transcription. RAR beta2 mRNA loss has often been detected in breast cancer tumors, whether promoter region methylation of the RAR beta2 gene accounts for its loss is still unknown. We examined the methylation status of RAR beta2 in breast tumors; 21 out of 50 (42%) breast tumors showed RAR beta2 hypermethylation. RT-PCR analysis showed a complete loss of RAR beta2 mRNA expression in 15 out of 43 (35%) breast tumors. No correlation between the hypermethylation and RAR beta2 loss was found, suggesting that hypermethylation is not fully responsible for the loss of expression of the RAR beta2 gene during breast tumorigenesis.