Persistent inequalities in 90-day colon cancer mortality: an English cohort study.

BACKGROUND: Variation in colon cancer mortality occurring shortly after diagnosis is widely reported between socio-economic status (SES) groups: we investigated the role of different prognostic factors in explaining variation in 90-day mortality. METHODS: National cancer registry data were linked with national clinical audit data and Hospital Episode Statistics records for 69 769 adults diagnosed with colon cancer in England between January 2010 and March 2013. By gender, logistic regression was used to estimate the effects of SES, age and stage at diagnosis, comorbidity and surgical treatment on probability of death within 90 days from diagnosis. Multiple imputations accounted for missing stage. We predicted conditional probabilities by prognostic factor patterns and estimated the effect of SES (deprivation) from the difference between deprivation-specific average predicted probabilities. RESULTS: Ninety-day probability of death rose with increasing deprivation, even after accounting for the main prognostic factors. When setting the deprivation level to the least deprived group for all patients and keeping all other prognostic factors as observed, the differences between deprivation-specific averaged predicted probabilities of death were greatly reduced but persisted. Additional analysis suggested stage and treatment as potential contributors towards some of these inequalities. CONCLUSIONS: Further examination of delayed diagnosis, access to treatment and post-operative care by deprivation group may provide additional insights into understanding deprivation disparities in mortality.

Major orthopaedic surgeries for haemophilia with inhibitors using rFVIIa.

SUMMARY: Between 2000 and 2008, 11 major orthopaedic surgeries for 7 congenital haemophilia patients with inhibitors were performed by the first author as the primary doctor using recombinant activated factor VII (rFVIIa). Orthopaedic surgical treatments were performed for six surgeries for four high-responder haemophilia A patients, three surgeries for two high-responder haemophilia B patients and two surgeries for one low-responder haemophilia B patient. This low-responder patient is allergic to factor IX products, so he usually uses rFVIIa as a haemostatic agent. All of the surgeries were major, such as joint arthroplasty, arthroscopic synovectomy, and a combination of both, and excellent surgical results were achieved. Seven cases were controlled by bolus infusion of rFVIIa, and the other four cases were controlled by combined bolus and continuous infusion of rFVIIa. An anti-fibrolytic agent was used for all cases. There were no thrombogenic adverse effects, only two bleeding episodes. As for haemostatic control, nine surgeries were excellent, one was good and one was fair. This report is the largest clinical report on major orthopaedic surgeries at a single institute. We have concluded that the combination of bolus and continuous infusion of rFVIIa is safe and effective, and more convenient to administer than simple bolus infusion therapy to achieve haemostasis at peri-operative periods. In addition, our data also concurs with the data of several previous reports which showed that orthopaedic surgery for haemophilia patients with inhibitors by means of rFVIIa is safe and effective.

[Infective endocarditis complicated with ruptured mycotic intracranial aneurysms].

A 38-year-old man was hospitalized complaining of an episode of syncope. He was diagnosed with acute infective endocarditis (IE) of the aortic and the mitral valves with mobile and large vegetations, complicated with mycotic cerebral emboli related to the left anterior and the middle cerebral arteries. Double valve replacement with mechanical prosthesis was performed within 24 hours after cerebral accident occurred. On the 36 postoperative day, emergency cerebrovascular surgery was done due to rupture of a mycotic intracranial aneurysm. He was discharged on foot without any neurological abnormal finding. The optimum treatment of IE complicated with cerebral embolism is a controversial theme. Management should be considered carefully in individual cases.

Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team.

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.

Long-term follow-up of childhood acute lymphoblastic leukemia in Tokyo Children's Cancer Study Group 1981-1995.

The objectives were as follows: Firstly, to estimate the overall probability of event-free survival (EFS) and isolated CNS relapse in the studies for children with acute lymphoblastic leukemia (ALL) during the 1980s and 1990s. Secondly, to report the EFS according to presenting features and lineage. Thirdly, to evaluate the treatment results re-classified by the risks of NCI criteria. Four consecutive protocol studies were performed in the Tokyo Children's Cancer Study Group: L81-10 protocol (1981-1984, 189 patients), L84-11 (1984-1989, 484 patents), L89-12 (1989-1992, 418 patients) and L92-13 (1992-1995, 347 patients). Overall EFS at 5 years in each protocol was 56.5 +/- 3.8(1 s.e.)%, 71.0 +/- 2.1%, 67.8 +/- 2.3%, and 63.4 +/- 2.7%, respectively. The cumulative isolated CNS relapse rate at 5 years was 8.1 +/- 2.1%, 3.5 +/- 0.9%, 3.6 +/- 1.0%, 1.0 +/- 0.6. The EFS in SR/HR (standard risk/high risk) according to the NCI criteria in B-precursor ALL at 5 years was 61.9 +/- 4.3%/41.4 +/- 7.4% (lineage was not confirmed.), 72.5 +/- 2.6%/63.4 +/- 5.0%, 77.4 +/- 2.7%/56.3 +/- 4.7%, and 67.8 +/- 3.4%/56.7 +/- 5.4% in each protocol. Also EFSs according to NCI SR/HR at 5 years of T-ALL in protocols L84-11, L89-12 and L92-13 were 55.6 +/- 16.6%/60.9 +/- 10.1%, 72.7 +/- 13.4%/51.6 +/- 9.1%, and 77.1 +/- 14.4%/53.6/10.1%, respectively. The truncation of maintenance therapy to 6 months resulted in a decreased EFS in L92-13, particularly due to an increase of bone marrow relapse after cessation of therapy in SR and HR. The NCI risk criteria work properly even in the patients treated by different intensities, so that it makes the comparison possible among the patients in various groups. The overall EFSs in childhood ALL improved in 1980s, but it seemed stable or decreased in 1990s. The short maintenance therapy resulted in poor outcome in SR on the L92-13 protocol. Many of these late relapsers were effectively rescued and overall survival remained at a high level. The proportion of patients who received cranial irradiation reduced without any increase of the CNS events.

Immunophenotypic and functional characterization of CD33(+)CD34(+) cells in human cord blood of preterm neonates.

OBJECTIVE: To characterize CD33(+)CD34(+) cells, a major population in human cord blood (CB) CD34(+) cells of preterm neonates. MATERIALS: The proportion of CD33(+) cells was analyzed on CB CD34(+) cells from preterm and full-term neonates. CD33(+)CD34(+) cells were purified by cell sorting and analyzed on their clonogenic activity, proliferative activity in short-time liquid suspension culture, and GATA-2 mRNA expression by RT-PCR and Southern blot. RESULTS: The absolute numbers and proportion of CD34(+) cells in mononuclear cells inversely correlated with gestational age. CD33 was expressed on a majority of CB CD34(+) cells of preterm neonates but on only a minor population of them in full-term neonates. In addition, CD33 was dominantly expressed on CD38(-)CD34(+) cells or CD117(low)CD34(+) cells in CB of preterm neonates. CD33(+)CD34(+) cells of preterm cord blood had high proliferative and reproducible potentials compared with CD33(-)CD34(+) cells. CD33(+)CD34(+) cells as well as CD33(-)CD34(+) cells from preterm CB highly expressed GATA-2, in contrast to those from BM. CONCLUSIONS: These results suggest that CD33(+)CD34(+) cells, which are a major population in CB CD34(+) cells of preterm neonates, do not simply represent relatively mature myeloid lineage hematopoietic progenitor cells as those in adult BM CD34(+) cells, and may contain hematopoietic stem cells or primitive progenitor cells as in fetal liver.

Effects of vasodilator agents on smooth muscle cells of the coronary artery of the pig.

1 Effects of the vasodilator agents, papaverine, diltiazem, and sodium nitroprusside (SNP) on the electrical and mechanical activities of the smooth muscles of the coronary artery of the pig were compared.2 At a concentration of 10(-5) M, papaverine hyperpolarized and increased the ionic conductance of the membrane, SNP slightly hyperpolarized but diltiazem had no effect on the membrane potential and membrane ionic conductance.3 At a concentration of 10(-5) M, diltiazem abolished the spike evoked by outward current pulses in the presence of tetraethylammonium (TEA) 10 mM, while papaverine and SNP slightly reduced spike amplitude.4 The K-induced contraction produced by any given concentration of [K](o) over 20.2 mM was suppressed by diltiazem and SNP dose-dependently in concentrations greater than 10(-6) M; higher concentrations of papaverine were required to suppress contraction.5 The acetylcholine (ACh)-induced contraction was suppressed by diltiazem and SNP at concentrations greater than 10(-6) M and by papaverine in concentrations over 10(-5) M.6 In saponin-treated skinned muscles, papaverine, diltiazem and SNP had no effect on the pCa-tension relationship, i.e. these agents had no effect on the Ca receptor of contractile proteins. Furthermore, the caffeine-induced contraction in skinned muscles (after Ca loading) was not affected by these agents, i.e. the mechanism of Ca release by caffeine in skinned muscles was not affected.7 Chlorpromazine, an agent interacting with calmodulin, antagonized the contractile effect of calcium on skinned muscle fibres.8 The results obtained are discussed in relation to spike and contraction generating mechanisms, i.e. the effects of these agents on Ca influx and Ca release from stored sites. The results indicated that at equimolar concentrations diltiazem suppressed the mechanical response in the coronary artery of the pig more than SNP or papaverine.

Increased sensitivity for detection of human cytomegalovirus in urine by removal of inhibitors for the polymerase chain reaction.

The presence of inhibitors in urine interferes with the enzymatic reaction of the polymerase chain reaction (PCR) for detection of human cytomegalovirus (HCMV). To remove inhibitors, HCMV virions in urine were precipitated with polyethylene glycol, or DNA was extracted from urine by the use of glass powder and subjected to PCR followed by Southern blot hybridization with alkaline phosphatase-linked oligonucleotide probes. These simple, rapid methods increased significantly the sensitivity of PCR for detection of HCMV in urine.

Evaluation of treatments for liver abscess: significance of intra-arterial antibiotic injection therapy.

Various treatments were performed in 14 patients with liver abscess, and their clinical effects were compared. The treatments were intra-arterial antibiotic infusion therapy (Group A, 4 patients), intra-arterial infusion therapy plus percutaneous drainage of the abscess (Group B, 4 patients), and intravenous antibiotics alone (Group C, 6 patients). The period from the beginning of treatment to negative conversion of CRP* (period until cure) was compared among the groups. Groups A and B had received intravenous antibiotics for a mean of 10 days and 16 days, respectively, but the treatment was ineffective. The mean period until cure from the beginning of intra-arterial infusion therapy was 36 days for Group A and 18 days for Group B. In Group C, the mean period until cure was 28 days. All patients recovered, and recurrence was observed in only one patient. Although liver abscess can be treated successfully in many patients by intravenous antibiotics alone, intra-arterial therapy is effective in those in whom intravenous therapy is not effective.

The choice of opiate receptor subtype by neo-endorphins.

The choice of opiate receptor subtype by alpha- and beta-neo-endorphin was studied in isolated preparations. Neo-endorphins had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum as well as on the rabbit vas deferens which had been shown to contain kappa-receptors exclusively. Mr 2266, a relatively specific kappa-receptor antagonist, was more effective than naloxone, a relatively mu-receptor antagonist, to antagonize the agonist actions of neo-endorphins in either the guinea-pig and rabbit ileum or in the rabbit vas deferens. By contrast, in the mouse vas deferens, the effectiveness of Mr 2266 to antagonize the agonist actions of neo-endorphins was low and similar to that of naloxone. The potencies of neo-endorphins relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in the guinea-pig ileum were similar to those in the rabbit ileum but were significant different from those in the mouse vas deferens. The data indicate that neo-endorphins act as kappa-receptor agonists in either the guinea-pig and rabbit ileum or in the rabbit vas deferens while in the mouse vas deferens they act on opiate receptor subtypes other than kappa- and mu-receptors.

Small hepatocellular carcinoma with intravascular tumor growth into the right atrium.

A 66-year-old man with ascites and marked edema in the lower extremities was suspected of having secondary Budd-Chiari syndrome due to primary liver cancer, based on imaging diagnosis, i.e., ultrasonography, computed tomography, and inferior venacavogram. At autopsy, an encapsulated small liver cancer was found to have extended into the inferior vena cava and right atrium. There have been few reports of small hepatocellular carcinoma with intravascular tumor growth into the right atrium.

Simple 13C-urea breath test with infra-red spectrophotometer.

When mass spectrophotometric analysis is used for the 13C-urea breath test to assess H. pylori infection, it is costly, complicated, and time-consuming. To overcome these disadvantages, we utilized an infra-red spectrophotometer as a substitute for the mass spectrophotometer. A total of 153 patients (181 tests) analyzed with peptic ulcers or non-ulcer dyspepsia were investigated. Breath samples were collected 15 min after ingestion of 13C-urea (100 mg in 30 ml water). An infra-red spectrophotometer was used to determine the concentration of 13CO2 in the expirate. The 13CO2/12CO2 ratio was also measured by mass spectrophotometry to compare results with those of infra-red spectrophotometric analysis. Direct detection of H. pylori was qualified in biopsy specimens. Of the 181 biopsies, 138 were positive for H. pylori infection and 43 were negative. With the urea breath test, the mean value in the positive group was significantly higher than that in the negative group (0.062 +/- 0.044 vs 0.011 +/- 0.014, respectively). The cut-off level, 0.01, was determined as delta 13C atom %. The sensitivity of infra-red spectrophotometry was 97.8% (135/138) and specificity was 74.4% (32/43). There was an extremely high coefficient of correlation (r = 0.996) between mass and infra-red photometric analysis. Infra-red spectrometry appears to have great potential not only for diagnosing H. pylori infection but also for assessing treatment results. Its advantages include technical simplicity, cost-effectiveness, and high accuracy.

CD18/CD54(+CD102), CD2/CD58 pathway-independent killing of lymphokine-activated killer (LAK) cells against glioblastoma cell lines T98G and U373MG.

For natural killer cell-mediated cytolysis (NK-lysis) and lymphokine-activated killer cell-mediated cytolysis (LAK-lysis), the co-stimulatory signals of CD18/CD54(+CD102) and CD2/CD58 pathways are essential. However, in this report, we describe a LAK-lysis that does not depend upon these two pathways. The killed cells were glioblastoma cell lines T98G and U373MG. The LAK cells were induced from peripheral blood lymphocytes in the presence of interleukin-2. 1) The T98G and U373MG did not express CD54 or CD102, but expressed CD58. 2) However, when they were pretreated with an anti-CD58 (TS2/9), the LAK-lysis was not blocked. 3) The LAK-lysis was markedly inhibited by pretreating with Concanamycin A and slightly inhibited by treating with antitumor necrosis factor-related apoptosis-inducing ligand (anti-TRAIL) antibody. 4) Nineteen percent of the LAK cells adhered to the T98G. The adhered LAK cells killed it. But nonadherent LAK cells could not kill the T98G or U373MG but killed lymphoblastoma cell lines Raji and NALM-6. These findings suggested that this type of the LAK-lysis might not depend upon the CD18/CD54(+CD102) pathway or CD2/CD58 pathway. The effector cells that killed the T98G and U373MG might not always be the same as the effector cells that killed the other cell lines. The LAK cells contain several subsets, and one of the subsets might kill these two target cell lines.

A lymphokine-activated killer (LAK)-resistant cell line, and low expression of adhesion molecules LFA-3 and VCAM-1 on its cell surface.

Tumor cell lines are generally killed by lymphokine-activated killer (LAK) cells. In this study, however, we report a LAK-resistant cell line, OKM-2T. The OKM-2T is an adult T-cell leukemia (ATL) cell line, and was compared to other ATL cell lines and non-ATL cell lines. The LAK cells were generated from healthy volunteers. Cell surface markers were determined by a flow cytometry test. The ATL and non-ATL cell lines were killed by the LAK cells, markedly or moderately. However, the OKM-2T was scarcely killed. The adhesion tendency of the OKM-2T to the LAK cells was preserved at the same level as that of the other cell lines, whereas the OKM-2T showed low levels of adhesion molecules CD58 (LFA-3), CD86, and CD106 (VCAM-1). We determined blocking tests using specific antibodies. Anti-CD58 blocked the LAK lysis. Anti-CD54 and anti-CD106 enhanced the blocking effect of the anti-CD58; anti-CD86 did not show such an effect. These results suggest that the low expression of CD58 in the OKM-2T may have an intimate relationship with LAK resistance, and that the low expression of CD106 may also be responsible for it, in part.

Relation of natural killer cell line NK-92-mediated cytolysis (NK-92-lysis) with the surface markers of major histocompatibility complex class I antigens, adhesion molecules, and Fas of target cells.

Natural killer (NK) cell line NK-92 has recently been established by Klingemann et al. In this study, we compared the NK-92-mediated cytolysis (NK-92-lysis) with the killing of healthy volunteers' NK cells and lymphokine-activated killer (LAK) cells. The NK-92-lysis was partially different from the NK- and LAK-lysis. 1) The NK-92 could kill most of major histocompatibility complex (MHC) class I antigen-positive tumor cells. 2) The NK cells killed a myeloid leukemia cell line K562, but the NK-92 showed low killer activity against it. 3) The LAK cells could not kill a CD58-deficient cell line OKM-2T, whereas the NK-92 could kill it sufficiently. 4) The NK-92 could not kill CD54-, CD102-deficient cell lines T98G and U373MG; however, the LAK cells could kill them. Blocking tests using specific antibodies revealed the reason for these differences. The K562 expressed relatively low levels of CD54 and CD102. When the K562 was pretreated with anti-CD54 and anti-CD102, the NK-92 could not kill it at all, whereas the NK cells could still kill it, although the killing level decreased. The NK-92 could not kill the anti-CD54- and anti-CD102-treated OKM-2T. The LAK cells could not kill anti-CD58-treated U373MG and T98G. These findings suggest that NK-92-lysis may require the CD54 and CD102 but that NK-lysis does not require them as much, whereas the LAK-lysis may be rather in relation with the CD58. The NK-92 has high killer activity, and may be applicable for clinical use. However, it should be considered that the NK-92 cannnot kill CD54-, CD102-deficient tumor cells.

Clinical analysis and prognostic study of ossified ligamentum flavum of the thoracic spine.

OBJECT: A variety of factors may affect surgery-related outcome in patients with ossification of the ligamentum flavum (OLF) of the thoracic spine. The aim of this study was to determine these factors on the basis of preoperative clinical and radiological findings. METHODS: The authors treated 31 cases of symptomatic thoracic OLF between 1988 and 1999. The following factors were retrospectively studied: patient age, sex, morbidity level, initial symptoms, chief complaint, duration of symptoms, patellar reflex, Achilles reflex, computerized tomography (CT) finding, presence of intramedullary change determined by magnetic resonance imaging, coexistent spinal lesions, preoperative grade, and postoperative grade. A decompressive laminectomy was performed in all cases. In 29 patients (94%) improved symptoms were demonstrated postoperatively. In terms of functional prognosis, the preoperative duration of symptoms was significantly shorter in the group of patients with excellent outcomes than in those with fair outcomes (p < 0.05). No significant difference was observed in the correlation between other factors. To evaluate the degree of preoperative thoracic stenosis and the severity/extent of OLF-induced spinal compression, we used an original OLF CT scoring system. A score of excellent on the CT scale tended to indicate an excellent prognosis (p < 0.01). CONCLUSIONS: Thoracic OLF frequently develops in the lower-thoracic spine in middle-aged men, and it is complicated by various spinal lesions in many cases. Early diagnosis and treatment are important for understanding the clinical symptoms and imaging diagnosis because the present findings suggest that a delay in diagnosis and treatment correlates with the functional prognosis postoperatively.

The choice of opioid receptor subtype in isolated preparations by dynorphins.

The choice of opioid receptor subtype by dynorphins was studied in isolated preparations. Both dynorphin-(1-17) and dynorphin-(1-8) had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum. The inhibition of contractions by dynorphin-(1-17) in three preparations was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors, indicating that dynorphin-(1-17) acted on kappa-receptors in three preparations. Additionally, the inhibitory potency of dynorphin-(1-17) relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in guinea-pig ileum was similar to that in either mouse vas deferens or rabbit ileum. This also suggested that dynorphin-(1-17) acted as a kappa-receptor agonist in three preparations. The effectiveness of naloxone and Mr 2266 to antagonize the agonist action of dynorphin-(1-8) indicated that dynorphin-(1-8) acted as a kappa-receptor agonist in either guinea-pig ileum or rabbit ileum whether or not peptidase inhibitors were existed while in mouse vas deferens it acted as a delta- or kappa-receptor agonist in the absence or presence of peptidase inhibitors, respectively. Thus, the choice of opioid receptor subtype in mouse vas deferens by dynorphin-(1-8) was likely to depend whether peptidases were inhibited or not. The inhibitory potency of dynorphin-(1-8) in the presence of peptidase inhibitors relative to that of ethylketocyclazocine in rabbit vas deferens, which had been shown to contain kappa-receptors exclusively, was similar to that in either mouse vas deferens or rabbit ileum, but was significantly different from that in guinea-pig ileum. This indicates that kappa-receptors in guinea-pig ileum are different from those in other preparations although the possibility of other causes such as incomplete inhibition of peptidase(s) can not be neglected.

Invasive subglottal aspergillosis in a patient with severe aplastic anemia: a case report.

A 19-year-old female with aplastic anemia who developed subglottal aspergillosis is reported. She presented with fever, cough and stridor. Inspiratory dyspnea progressed rapidly and emergent tracheostomy was performed, which confirmed the diagnosis. In spite of intensive anti-fungal treatment combined with adoptive immunotherapy, Aspergillus infection expanded and she died of pulmonary aspergillosis. Autopsy revealed the fungal mass obstructing the trachea and disseminated pulmonary aspergillosis. Difficulties in diagnosis and management of subglottal Aspergillus infection are discussed.

Treatment of Langerhans cell histiocytosis in children with etoposide.

Ten children with Langerhans cell histiocytosis (LCH) were treated with etoposide. For five patients, this was the initial diagnosis. The other five had failed to respond to previous therapies. Etoposide (100 mg/m2) was given intravenously twice a week for 4 weeks, followed by maintenance therapy every 2 to 4 weeks for 2 years. All 10 patients responded to etoposide, and 6 of them (60%) have been in complete remission for 3 to 36 months without any side effects. One patient relapsed with diabetes insipidus, one with a soft tissue mass, and two others developed multiple bone lesions. Chemotherapy with etoposide appears to be effective and safe for the treatment of children with systemic LCH.