Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.     

Comparison between published clinical success of direct resin composite restorations in vital posterior teeth in 1995–2005 and 2006–2016 periods

Composites are increasing in popularity as restorative materials. This growing role indicates the necessity of studies on their clinical outcome. In this study, clinical studies published on the performance of posterior composite restorations were included except those of less than a 24‐month assessment period. Results of non‐vital, anterior or primary teeth and cervical single‐surface restorations were also excluded. Records about composite type, number of final recall restorations, failure/survival rate, assessment period and failure reasons were analysed for each decade. Overall survival/failure rates for studies in 1995–2005 were 89.41%/10.59% and for 2006–2016 were 86.87%/13.13%, respectively. In 1995–2005, the reasons for failure were secondary caries (29.47%) and composite fracture (28.84%) with low tooth fracture (3.45%) compared with reasons of failure in 2006–2016, which were secondary caries (25.68%), composite fracture (39.07%), and tooth fracture (23.76%). An increase in incidence of composite fracture, tooth fracture and need for endodontic treatment as failure reasons was noted in the latter decade in addition to a decrease in secondary caries, postoperative sensitivity, unsatisfactory marginal adaptation and wear. The overall rates of failure showed little difference, but the causes showed a notable change. This is believed to be a reflection of increased use of composites for larger restorations and possibly changes of material characteristics.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Multiple forms of acid phosphatase activity in Gaucher's disease.

Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to those of the major acid phosphatase activity observed to be present in serum of patients with Gaucher's disease. These data indicate that simple spleen spillage cannot account for the increased levels of serum acid phosphatase in patients with Gaucher's disease.     

Serologic tests in the diagnosis of systemic candidiasis. Enhanced diagnostic accuracy with crossed immunoelectrophoreses.

In order to assess the diagnostic value of serologic methods in discriminating between colonization and disseminated infection with Candida species, serum samples from 201 consecutive patients receiving parenteral hyperallmentation were examined for the presence of agglutinating and precipitating antibodies to Candida albicans. In these patients, fungal colonization was detected in 50 per cent, transient fungemia in 6 per cent and disseminated candidlasis in 2.5 per cent. Agglutinating antibodies were of no diagnostic value in separating patients with Candida colonization from those with disseminated infection (sensitivity ? 75 per cent, predictive value ? 20 per cent). Serum Candida precipitins were detected by double immunodiffusion (DID) in all five patients with systemic candidiasis (100 per cent sensitivity); however, since only five of 53 patients with precipitins detected by DID demonstrated evidence of systemic candidiasis, the predictive value of the test was unacceptably low (9 per cent). When the serums which were positive by DID were submitted to crossed immunoelectrophoresis (XIE), precipitin bands to antigens other than mannan were obtained in only nine patients, including all five patients with disseminated candidiasis. Thus, detection by XIE of serum Candida precipitins directed against antigens other than mannan was associated with a predictive value of 56 per cent and a sensitivity of 100 per cent. The detection of serum Candida precipitins by DID is a sensitive screening test in patients at high risk for the development of systemic candidiasis; patients with persistently negative precipitins by DID are unlikely to harbor disseminated candidiasis. If precipitin bands are detected by XIE to antigens other than mannan, there is a high likelihood that the patient has disseminated or invasive Candida infection.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

世界胃肠病学组织(WGO-OMGE)临床指南——发展中国家幽门螺杆菌感染

我非常高兴向大家推荐这份发展中国家幽门螺杆菌（H．priori）临床指南。该指南的编译是由数位在该领域具有丰富临床经验的世界知名专家共同完成的。     

Identification of Bakb, a new platelet-specific antigen associated with posttransfusion purpura

Baka is a platelet alloantigen whose putative allele, Bakb, has not been identified previously. By using a serum, "Har," obtained from a patient with posttransfusion purpura, we describe the platelet alloantigen Bakb. The Har serum reacted with an NP-40-extractable platelet membrane protein of 142 kd with mobility similar to platelet glycoprotein IIb alpha. We found that the antigen recognized by the Har serum is inherited in an autosomal dominant mode with an apparent gene frequency of .39. Chi-square analysis of observed and expected phenotype frequencies indicated that serum Har recognizes Bakb, the anticipated allele of Baka. Our findings provide new evidence for polymorphism of glycoprotein IIb and for the association of posttransfusion purpura with alloimmunization to determinants on this glycoprotein.     

Association of the subtype 2 of the Epstein-Barr virus with T-cell non- Hodgkin's lymphoma of the midline granuloma type [see comments]

Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration. Using EBV-RNA (EBER) in situ hybridization and EBV polymerase chain reaction (PCR), we have looked for the presence of EBV in six LMGs and six non-Hodgkin's lymphomas (NHLs) located in the nasopharyngeal region, and determined the subtype of EBV. Six of six LMGs were positive by PCR and EBER in situ hybridization, whereas NHLs were either negative or, in three of six cases, showed few EBER- positive cells considered to be nonneoplastic lymphocytes. The subtype 2 was found in LMG lesions of three of six patients; the remaining three of six patients with LMG had the generally occurring subtype 1. The results indicate that the association of EBV with NHL may depend more on tumor type than on its localization. The occurrence of the rare subtype 2 in LMG may relate to a covert immune defect.     

Self-Efficacy,Depression, and Self-Care Activities in Adult Jordanians with Type 2 Diabetes: The Role of Illness Perception

Diabetes mellitus is reaching epidemic levels worldwide. In a developing country like Jordan, type 2 diabetes mellitus (T2DM) has reached a prevalence rate of 17.1%. This cross-sectional study examined the relationship between self-care activities and: illness perception, depression, social support, religiosity and spiritual coping, and self-efficacy among patients with T2DM. A random sample of 220 patients with T2DM, who attended Jordan University Hospital in Jordan were enrolled. The data were collected through a structured interview and the medical files. The instruments consisted of a sociodemographic and clinical standardised questionnaires: Brief Illness Perception Questionnaire, Patients’ Health Questionnaire-9; ENRICH Social Support Instrument; Religious and Spiritual Coping Subscale; Diabetes Management Self-Efficacy Scale; and Summary of Diabetes Self-Care Activities. Bivariate analysis investigated the relationship between variables. Structure Equation Modelling (SEM) was performed to test the proposed conceptual model. The study found that approximately 70% of the respondents suffered some form of depressive symptoms. The SEM showed a direct relationship between self-efficacy and self-care activities (β = 0.40; p < 0.001). Depression was indirectly related to self-care activities through self-efficacy (β = –0.20; p = 0.003); nevertheless, it was directly related to perception of: treatment control, consequences, and emotional representations. Overall, the sequence between illness perception and self-efficacy was mediated by depression. Strategies to promote self-efficacy and illness perception are vital in customising a diabetes health plan to meet Arabic cultural expectations.