[Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma].

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Clinical and genetic features of Chinese patients with lichen and macular primary localized cutaneous amyloidosis.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic skin disorder. The genetic basis of familial (f)PLCA involves mutations in the oncostatin M receptor (OSMR) and interleukin-31 receptor A (IL31RA) genes, but the disease pathophysiology is not fully understood. AIM: To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China. METHODS: This study was carried out on 64 patients with sPLCA, along with 36 with fPLCA and 10 unaffected individuals collected from 23 unrelated Chinese families. Genomic DNA was extracted from peripheral blood samples. Mutation screening of 17 OSMR exons was performed by Sanger sequencing. RESULTS: PLCA lesions are typically localized to the shins, forearm and back. Sequence analysis of OSMR exons demonstrated that the OSMR missense mutation rate in patients with fPLCA (63.89%) was significantly higher than that in patients with sPLCA (34.38%). The male/female ratio of patients carrying a homozygous OSMR mutation (0.29) was significantly lower than that of patients carrying a heterozygous OSMR mutation (1.08; P < 0.05) and of patients with wildtype OSMR (1.75; P < 0.01). Age of onset of PLCA with OSMR homozygous mutation (median age 20 years) was earlier than that of PLCA with OSMR heterozygous mutation (median age 32 years; P < 0.01) or PLCA with wildtype genotype (median age 32 years; P < 0.01). CONCLUSION: The present data indicate OSMR mutations as not only the main cause of fPLCA, but also the potential source of the pathogenesis of sPLCA, although the exact molecular mechanism remains unknown.

Revealing homogeneous plastic deformation in dendrite-reinforced Ti-based metallic glass composites under tension.

The tensile plastic deformation of dendrite-reinforced Ti-based metallic glass composites (MGCs) was investigated. It was found that there is a critical normalized strain-hardening rate (NSHR) that determines the plastic stability of MGCs: if the NSHR is larger than the critical value, the plastic deformation of the MGCs will be stable, i.e. the necking and strain localization can be effectively suppressed, resulting in homogeneous plastic elongation. In addition, dendrite-reinforce MGCs are verified as being intrinsically ductile, and can be used as good coatings for improving the surface properties of pure titanium or titanium alloys. These findings are helpful in designing, producing, and using MGCs with improved performance properties.

[Clinical study of 131 children with multi-system Langerhans cell histiocytosis].

OBJECTIVE: To analyze the clinical characteristics and treatment outcome of children with multi-system Langerhans cell histiocytosis (MS-LCH). METHOD: From January 2007 to December 2013, newly diagnosed patients with histopathologically-confirmed MS-LCH were enrolled in this retrospective study. All patients were treated on the Shanghai Children's Medical Center LCH protocol (LCH-Ⅱ modified protocol). Survival was determined using the Kaplan-Meier method with differences between different groups compared using the Log-Rank test. Prognostic relevance of different parameters were analyzed by Cox proportional hazard model. RESULT: Of the 131 patients (86 boys and 45 girls), the median age was 3 years (range 3 months to 14 years). Rapid response at week 6 was achieved in 79% (104/131) evaluable patients and 74% patients (48/65) with risk organ involvement. The 3-year event free survival (EFS) and 3-year overall survival (OS) for all cases were (62±5)% and (82±4)%. The 3-year OS was significantly different between age at diagnosis ≤2 years and >2 years group.The 3-year OS was also significantly different between patients with and without risk organ involvement.The 3-year OS of patients who had rapid response at week 6 was significantly higher than that of those without rapid response (χ(2) =12.600, 11.583, 38.711; P=0.000, 0.001, 0.000). Cox regression analysis showed that risk organ involvement and poor response at week 6 were the most important prognostic factors for patients with MS-LCH (OR=12.352, 14.356; P=0.001, 0.000). However, age was not the independent prognostic risk factor (OR=1.013, P=0.207). There were 36 patients (28%, 36/131) who experienced disease progression or relapse. The time to disease progression or relapse ranged from 1 to 25 months from the initial diagnosis (median 11 months). Significantly lower OS (18±3)% was observed in 20 patients with risk organ involvement at progression or relapse. Patients with poor response at week 6, younger age or risk organ involvement at diagnosis was associated with disease progression/relapse (χ(2)=15.747, 7.289, Z=3.865; P=0.000, 0.007, 0.000). CONCLUSION: Risk organ involvement and poor response at week 6 are the strongest prognostic factors for patients with MS-LCH. Second initial treatment for patients with poor response at week 6 and effective salvage therapy need to be taken into account in our future studies.

Loading-rate-independent delay of catastrophic avalanches in a bulk metallic glass.

The plastic flow of bulk metallic glasses (BMGs) is characterized by intermittent bursts of avalanches, and this trend results in disastrous failures of BMGs. In the present work, a double-side-notched BMG specimen is designed, which exhibits chaotic plastic flows consisting of several catastrophic avalanches under the applied loading. The disastrous shear avalanches have, then, been delayed by forming a stable plastic-flow stage in the specimens with tailored distances between the bottoms of the notches, where the distribution of a complex stress field is acquired. Differing from the conventional compressive testing results, such a delaying process is independent of loading rate. The statistical analysis shows that in the specimens with delayed catastrophic failures, the plastic flow can evolve to a critical dynamics, making the catastrophic failure more predictable than the ones with chaotic plastic flows. The findings are of significance in understanding the plastic-flow mechanisms in BMGs and controlling the avalanches in relating solids.

[The effect of CPAP therapy on dizziness].

Objective:To implore the effect of continuous positive airway pressure (CPAP) therapy on dizziness patients and its mechanism. Method:Seventy-five dizziness patients were enrolled. All patients accepted polysomnographic test, dizziness handicap inventory, Pitsburgh sleep quality index and Epworth sleepiness scale before and after CPAP therapy. Patients were divided into two groups according to a polysomnographic test: OSAHS group (AHI≥15) and without OSAHS group (AHI<15); divided into three groups according to dizziness handicap inventory score: mild dizziness group (00.05), but CPAP therapy could ameliorate sleep disorder of the OSAHS group. ③Different levels of dizziness had no impact on improving DHI during CPAP therapy. However, the effect on sleep improvement decreased when patients had heavier dizziness. ④Treating by CPAP after three months could significantly improve patients dizziness (P<0.01). ⑤The dizziness of the patients in younger old group and old group have significant improvement after CPAP therapy (P<0.01). However, only younger old group has better sleep. Conclusion:CPAP therapy could dramatically improve dizziness in patients with sleep disorders.

Achieving high energy absorption capacity in cellular bulk metallic glasses.

Cellular bulk metallic glasses (BMGs) have exhibited excellent energy-absorption performance by inheriting superior strength from the parent BMGs. However, how to achieve high energy absorption capacity in cellular BMGs is vital but mysterious. In this work, using step-by-step observations of the deformation evolution of a series of cellular BMGs, the underlying mechanisms for the remarkable energy absorption capacity have been investigated by studying two influencing key factors: the peak stress and the decay of the peak stress during the plastic-flow plateau stages. An analytical model of the peak stress has been proposed, and the predicted results agree well with the experimental data. The decay of the peak stress has been attributed to the geometry change of the macroscopic cells, the formation of shear bands in the middle of the struts, and the "work-softening" nature of BMGs. The influencing factors such as the effect of the strut thickness and the number of unit cells have also been investigated and discussed. Strategies for achieving higher energy absorption capacity in cellular BMGs have been proposed.

Identification of a locus characteristic of male individuals of buffalo grass [Buchloe dactyloides (Nutt.) Engelm.] by using an RAPD marker.

Buffalo grass [Buchloe dactyloides (Nutt.) Engelm.] plants can be either male, female, or hermaphrodite (monoecious). As there is no morphological difference in the early vegetative growth of these three classes of plants, it is worthwhile to use molecular biological methods to attempt to identify the sex of a plant at this early growth period. In this study, we identified 23 plants that had a stable sex for over at least 3 years. Of these, 9 were male plants, 10 were female plants, and 4 were hermaphrodites. Screening of 300 RAPD primers identified a primer, namely S211 (5'-ttccccgcga-3'), which is capable of identifying male plants. The specific fragment was cloned, sequenced, and submitted to the GenBank database (accession No. JN982469). When used to identify the sex of 188 plants during their first growing season, the S211 primer correctly identified 85.8% of all male plants. Our results showed that the S211 primer can identify the male, and in doing so, it facilitates buffalo grass breeding work.

Superelongation and atomic chain formation in nanosized metallic glass.

Bulk metallic glasses are brittle and fail with no plastic strain at room temperature once shear bands propagate. How do metallic glasses deform when the size is less than that of shear bands? Here we show that Al90Fe5Ce5 metallic glass with a size <20 nm can be extremely elongated to ∼200%. Remarkably, even an atomic chain was formed after sample necking, which was never observed in metallic glasses. The unexpected ductility may originate from the fast surface diffusion and the absence of shear band formation, and may guide the development of ductile metallic glasses for engineering applications.

A new mutation in a family with cold-aggravated myotonia disrupts Na(+) channel inactivation.

OBJECTIVE: To identify the molecular and physiologic abnormality in familial myotonia with cold sensitivity, hypertrophy, and no weakness. BACKGROUND: Sodium channel mutations were previously identified as the cause of several allelic disorders with varying combinations of myotonia and periodic paralysis. A three-generation family with dominant myotonia aggravated by cooling, but no weakness, was screened for mutations in the skeletal muscle sodium channel alpha-subunit gene (SCN4A). METHODS: Single-strand conformation polymorphism was used to screen all 24 exons of SCN4A and abnormal conformers were sequenced to confirm the presence of mutations. The functional consequence of a SCN4A mutation was explored by recording sodium currents from human embryonic kidney cells transiently transfected with an expression construct that was mutated to reproduce the genetic defect. RESULTS: A three-generation Italian family with myotonia is presented, in which a novel SCN4A mutation (leucine 266 substituted by valine, L266V) is identified. This change removes only a single methylene group from the 1,836-amino-acid protein, and is present in a region of the protein previously not known to be critical for channel function (domain I transmembrane segment 5). Electrophysiologic studies of the L266V mutation showed defects in fast inactivation, consistent with other disease-causing SCN4A mutations studied to date. Slow inactivation was not impaired. CONCLUSIONS: This novel mutation of the sodium channel indicates that a single carbon change in a transmembrane alpha-helix of domain I can alter channel inactivation and cause cold-sensitive myotonia.

Failure of screening to detect HIV in a foreign laborer who died of toxoplasmosis of the central nervous system.

The most common neurologic complication in patients with acquired immunodeficiency syndrome (AIDS) is cerebral toxoplasmosis. Patients with cerebral toxoplasmosis have characteristic findings on clinical examination and neuroimaging. They require prolonged treatment and have a considerable mortality rate. We report a case of cerebral toxoplasmosis in a foreign laborer with AIDS, in whom a human immunodeficiency virus (HIV) screening test failed to detect-HIV infection. The patient, a 23-year-old man from Thailand, presented in a confused state 2 weeks after his arrival in Taiwan. Computed tomography showed a mass effect, and magnetic resonance imaging showed multiple ring-enhanced lesions in the cerebrum. Serologic tests were positive for anti-HIV antibody and also showed high anti-Toxoplasma immunoglobulin G titers. Although symptomatic treatment was initiated, the patient's condition deteriorated rapidly and he died of multiple organ failure due to brain stem herniation a few days after admission. As the number of foreign laborers working in Taiwan has increased dramatically in recent years, the issues raised by this case are the efficacy of our screening protocols for foreign laborers and the increased occupational hazards encountered by medical personnel in Taiwan.

The major immunogenic epitopes of Epstein-Barr virus (EBV) nuclear antigen 1 are encoded by sequence domains which vary among nasopharyngeal carcinoma biopsies and EBV-associated cell lines.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a protein expressed consistently in EBV-infected cells and EBV-associated malignant tissues. A panel of monoclonal antibodies (MAbs) was generated against the C terminus of EBNA-1 and evaluated for the detection of EBNA-1 in different cell lines. The epitopes recognized were mapped. Since sequence variations of EBNA-1 have been reported in nasopharyngeal carcinoma (NPC) tissues and in infected healthy individuals, the ability of these MAbs to recognize a recombinant protein derived from an NPC biopsy was also analysed. MAb 4H11 appeared to react with EBNA-1 sequences from different sources, whereas MAbs 5C11, 5F12 and 8F6 failed to recognize a recombinant EBNA-1 protein cloned from an NPC patient. Using different recombinant EBNA-1 fragments in an immunoblot format, this study demonstrates that the domain bounded by amino acids 408 and 498 is very immunogenic in mice in that epitopes in this region are recognized by various MAbs. Amino acid sequences of EBNA-1 were also deduced from nucleotide sequences amplified from three Burkitt's lymphoma cell lines, two spontaneous lymphoblastoid cell lines, two NPC biopsies and one NPC hybrid cell line, NPC-KT, and compared to the sequence from B95-8. The amino acid sequence of EBNA-1 in Akata is almost identical to that in an NPC biopsy, except for amino acid 585. The results of this study indicate that the immunogenic epitopes of EBNA-1 are highly variable.

A PCR Assay to Identify and Distinguish Single Juveniles of Meloidogyne hapla and M. chitwoodi.

Random amplified polymorphic DNA (RAPD) bands that distinguish Meloidogyne hapla and M. chitwoodi from each other, and from other root-knot nematode species, were identified using a series of random octamer primers. The species-specific amplified DNA fragments were cloned and sequenced, and then the sequences were used to design 20-mer primer pairs that specifically amplified a DNA fragment from each species. Using the primer pairs, successful amplifications from single juveniles were readily attained. A mixture of four primers in a single PCR reaction mixture was shown to identify single juveniles of M. hapla and M. chitwoodi. To confirm specificity, the primers were used to amplify DNA from several isolates of M. hapla that originated from different crops and locations in North America and also from isolates of M. chitwoodi that differed in host range. In characterizing the M. hapla isolates, it was noted that there was a mitochondrial DNA polymorphism among isolates for cleavage by the restriction endonuclease DraI.

Anomalous pulmonary venous pathway traversing pulmonary parenchyma. Diagnosis and implication.

STUDY OBJECTIVES: To describe four patients having total anomalous pulmonary venous connection with an intrapulmonary vertical vein, rendering difficulty in diagnosis and surgery. SETTING: a tertiary referral center. PATIENTS AND METHODS: By reviewing medical records, 4 of 25 patients with right atrial isomerism and total anomalous pulmonary venous connection were identified to have an intrapulmonary vertical vein. All four patients underwent echocardiography, catheterization, and angiography. One underwent MRI. Two underwent open-heart surgery and one received a modified Blalock-Taussig shunt. RESULTS: Right atrial isomerism was present in all four patients. On chest x-ray films, an abnormal shadow resembling scimitar syndrome was seen in two patients. Imaging the vertical vein was unsuccessful with an echocardiogram in all four patients. The intrapulmonary course of the vertical vein was depicted with a pulmonary venogram in two patients and with magnetic resonance in one patient. The intrapulmonary segment remained undetected until autopsy in one patient. All four patients died. At autopsy, the pulmonary venous confluence was hypoplastic in all four hearts. The vertical vein was buried in pulmonary parenchyma and drained to superior vena cava with significant obstruction. CONCLUSION: In the presence of right atrial isomerism and total anomalous pulmonary venous connection, there may be an intrapulmonary pulmonary venous connection that may be obstructed. Anastomosing the pulmonary venous confluence to the atrium may be difficult because of hypoplasia of the pulmonary venous confluence.

Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever.

OBJECTIVE: To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF). STUDY DESIGN: We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained. SUBJECTS: Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers. RESULTS: True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%. CONCLUSIONS: This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.

Mediastinal lymphangioma in an infant.

Lymphangioma confined exclusively to the mediastinum occurs rarely in patients under 2 years of age. A 17-month-old girl presented with recurrent respiratory symptoms and signs. Chest radiographs taken at 9 and 17 months of age showed a large mediastinal mass, which had increased in size during the interval. Sonography revealed the mass to be cystic and multiloculated. Magnetic resonance imaging demonstrated a heterogeneous mass lying in the anterior and superior mediastinum and enveloping the great vessels. The child underwent a left thoracotomy and the tumor was almost completely removed. The pathologic diagnosis was cavernous lymphangioma. The postoperative course was uneventful. Lymphangioma, though rare, should be considered in the differential list of mediastinal tumors and cysts in infants.

Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks.

OBJECTIVE: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis. METHODS: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively. RESULTS: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05). CONCLUSIONS: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended.

Kinetics of the reduction of cytochrome b5 with mutations in its membrane-binding domain.

In an attempt to understand which amino acids in the membrane anchor of cytochrome b5 might be determinants of its ability to support the cytochrome P450-catalyzed oxidation of selected substrates, the synthetic rat cytochrome b5 gene has been mutated by site-directed mutagenesis. The mutant proteins have been expressed in Saccharomyces cerevisiae, purified and assayed for their ability to support the cytochrome P450-catalyzed metabolism of the cytochrome b5 requiring substrate methoxyflurane (G. Vergères and L. Waskell, 1992, J. Biol. Chem. 267, 12583-12591). The rate of reduction of the cytochromes b5 by cytochrome P450 reductase has been examined by stopped-flow spectrophotometry to determine whether an altered rate of reduction of cytochrome b5 could explain the observed activity of cytochrome b5 in the purified reconstituted mixed-function oxidase system. A mutant in which the 22-amino-acid membrane anchor was replaced by a sequence of 22 leucines was unable to support methoxyflurane metabolism in the reconstituted system and was reduced by cytochrome P450 reductase at a rate (k = 4.5 x 10(-3) s-1) slow enough to explain this finding. Comparison of the rate of reduction of this mutant cytochrome b5 in 0.025% Tergitol and 40 microM dilauroylphosphatidylcholine suggests that this slow rate of reduction may be explained partially by aggregation of the polyleucine protein. The Pro115Stop mutant protein, which has been truncated by 19 amino acids in its COOH terminus resulting in a protein with one-half of the putative membrane anchor, supports methoxyflurane oxidation at 12-20% of the rate of the wild type protein. In addition it is reduced by cytochrome P450 reductase at a rate which should be capable of supporting a normal rate of production formation. The fact that the Pro115Stop mutant can be reduced at a rate capable of supporting a normal rate of methoxyflurane oxidation but in fact only supports methoxyflurane oxidation at 30% of the normal rate suggests that the mutant protein is deficient in its interactions with cytochrome P450. The mutant proteins, Pro115Ala and Ala116Pro, behaved essentially as did the wild type protein demonstrating that the presence (Pro115Ala) or absence (Ala116Pro) of an alpha helix in the middle of the putative membrane-binding domain of cytochrome b5 was not a determinant of the interaction of cytochrome b5 with cytochrome P450 reductase and cytochrome P450.(ABSTRACT TRUNCATED AT 400 WORDS)