Repeated isolation of Cryptococcus laurentii from the oropharynx of an immunocompromized patient

Cryptococcus laurentii is one of the non-neoformans cryptococci that have rarely been isolated from humans. We report a case of repeated colonization of the oropharynx by Cr. laurentii in a patient with erythroleukaemia. The isolate was identified by phenotypic and genotypic tests and showed resistance to fluconazole. This revised version was published online in June 2006 with corrections to the Cover Date.     

A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.     

Non-Healing Ulcer Due to Trichosporon loubieri in an Immunocompetent Host and Review of Published Reports

We report here a case of non-healing ulcer due to Trichosporon loubieri in an apparently immunocompetent female. The identity of isolate was confirmed by DNA sequencing of D1/D2 region of 26S rDNA. The minimum inhibitory concentrations of the isolate were amphotericin B—0.5 μg/ml; fluconazole—4 μg/ml; posaconazole—0.25 μg/ml; voriconazole—0.06 μg/ml. The patient was managed by extensive debridement and oral fluconazole 150 mg daily for 6 weeks. She responded to therapy. To the best of our knowledge, till date, this is the fourth report of human infection due to T. loubieri and the first of its kind in an immunocompetent host. A review of published literature on infections due to T. loubieri is also included.     

First Case of <Emphasis Type="Italic">Trichophyton soudanense</Emphasis> Isolated in Tunisia

This is a first case of Trichophyton soudanense isolated from Ivoiran student in Tunisia. A 24-year-old man was addressed for extensive erythematous, scaling lesions. Examination disclosed tinea capitis, tinea corporis, tinea pedis, and onychomycosis of toenails and fingernails. Isolates were identified as Trichophyton soudanense on the basis of macroscopy and microscopy colony characteristics. The patient was treated with fluconazole, topical econazole, and ciclopiroxolamine varnish. Although T. soudanense was identified since the late 1950s outside the African continent especially in the North America, Brazil, Australia, and many European countries, this is the first case reported in Tunisia. Accessibility to our universities for African students makes possible the emergence of this dermatophyte.     

梗阻性黄疸患者经内镜逆行胰胆管造影术后胆道感染的病原菌分布、耐药性及影响因素分析

目的:探讨梗阻性黄疸患者经内镜逆行胰胆管造影(ERCP)术后胆道感染病原菌分布、耐药性以及导致术后胆道感染的影响因素。方法:选择2016年3月至2019年10月我院收治的310例行ERCP治疗的梗阻性黄疸患者,根据ERCP术后是否发生胆道感染将其分为感染组(50例)和未感染组(260例)。检测胆道感染患者病原菌种类及其耐药性,多元Logistic回归分析影响梗阻性黄疸患者ERCP术后胆道感染的影响因素。结果:ERCP术后胆道感染发生率为16.13%,大肠埃希菌、铜绿假单胞菌、粪肠球菌、屎肠球菌是主要致病菌,检出率分别为40.79%、13.16%、9.21%、6.58%。大肠埃希菌、铜绿假单胞菌对头孢类、氨基糖苷类抗生素耐药率高,粪肠球菌、屎肠球菌对利福平、喹诺酮类抗生素耐药率高,大肠埃希菌、铜绿假单胞菌、粪肠球菌、屎肠球菌均对利奈唑胺、亚胺培南敏感。多元Logistic回归分析结果显示,恶性病变、ERCP2次及以上、胆胰管汇流异常、术后胆管引流不畅是梗阻性黄疸患者ERCP术后胆道感染的危险因素(P0.05),术后预防性使用抗生素是保护因素(P0.05)。结论:梗阻性黄疸患者ERCP术后存在一定胆道感染风险,革兰氏阴性菌是主要致病菌,临床应注重对高危因素预防,有必要术后选择敏感抗生素预防性治疗。     

Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release

Two groups of fluconazole mucoadhesive buccal discs were prepared: (a) Fluconazole buccal discs prepared by direct compression containing bioadhesive polymers, namely, Carbopol 974p (Cp), sodium carboxymethyl cellulose (SCMC), or sodium alginate (SALG) in combination with hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC). (b) Fluconazole buccal discs prepared by freeze drying containing different polymer combinations (SCMC/HPMC, Cp/HPMC, SALG/HPMC, and chitosan/SALG). The prepared discs were evaluated by investigating their release pattern, swelling capacity, mucoadhesion properties, and in vitro adhesion time. In vivo evaluation of the buccal disc and in vivo residence times were also performed. Fluconazole salivary concentration after application of fluconazole buccal systems to four healthy volunteers was determined using microbiological assay and high-performance liquid chromatography. SCMC/HPMC buccal disc prepared by direct compression could be considered comparatively superior mucoadhesive disc regarding its in vitro adhesion time, in vivo residence time, and in vitro/in vivo release rates of the drug. Determination of the amount of drug released in saliva after application of the selected fluconazole disc confirmed the ability of the disc to deliver the drug over a period of approximately 5 h and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.     

Microbiological Characteristics and Susceptibility Patterns of Strains of Rhodotorula Isolated from Clinical Samples

The members of the genus Rhodotorula show a marked ubiquity. In man, they have been isolated from faeces, nails, skin, sputum, digestive tract and adenoids, forming part of the normal human flora, although in recent years cases have been reported of both local and systemic infection by this yeast. There are virtually no studies in the literature on the sensitivity of this genus to the antifungal agents in common clinical use. Therefore, it is considered of interest to study the microbiological characteristics and the susceptibility patterns of Rhodotorula isolated from clinical samples. A total of 35 different strains of Rhodotorula were studied. In vitro susceptibility testing to 5-fluorocytosine, amphotericin B, ketoconazole, fluconazole and itraconazole was performed. All the strains were considered sensitive to 5-fluorocytosine, amphotericin B, ketoconazole and itraconazole and resistant to fluconazole. As a conclusion, we can state that all the antifungal agents tested, except fluconazole, are useful medicaments for the treatment of infections by the Rhodotorula genus. This revised version was published online in June 2006 with corrections to the Cover Date.     

Coccidioidomycosis of the male reproductive tract

Coccidioides immitis infection of the male reproductive tract is a rare entity that can evade diagnosis and pose a dilemma in management. Initially, patients are often evaluated for malignancy or other infections such as tuberculosis. In the past, surgery was the only management option for C. immitis infection of the male reproductive tract, but azole therapy now provides an adjunct or an alternative. We describe two patients who received azole therapy for C. immitis infection of the male reproductive tract. One received fluconazole for prostatic disease, while one received surgery followed by itraconazole for testicular disease. After 12 months of therapy, both remain asymptomatic and have decreased antibody titers against C. immitis.Disclaimer: The Views expressed herein are those of the authors do not reflect the official policy or position of the Department of the Air Force, Department of the Army, Department of Defence, or the U.S. Government.     

Novel technique for biliary reconstruction using an isolated gastric tube with a vascularized pedicle: a live animal experimental study and the first clinical case

Background

Biliary tract reconstruction continues to be a challenging surgical problem. Multiple experimental attempts have been reported to reconstruct biliary defects with different materials and variable outcome. Our aim was to evaluate a new method for biliary reconstruction using an isolated pedicled gastric tube in a live animal trial and also to present the first clinical case.

Methods

Seven mongrel dogs underwent biliary reconstruction using gastric tube harvested, completely separated from the greater curvature, and based on a vascularized pedicle with the right gastroepiploic vessels. The tube was interposed between the common bile duct (CBD) and the duodenum. Postoperative mortality, morbidity, liver functions, gross and microscopic histological picture were assessed. The first clinical case was also presented where, in a patient with post-cholecystectomy biliary injury, an isolated pedicled gastric tube was interposed between the proximal and distal ends of the CBD.

Results

One dog did not recover from anesthesia and another one died postoperatively from septic peritonitis. Five dogs survived the procedure and showed uneventful course and no cholestasis. The mean anastomotic circumference was 4.8 mm (range 4-6) for CBD anastomosis and 6.2 mm (range 5-7) for duodenal anastomosis. Histologically, anastomotic sites showed good evidence of healing. In the first clinical case, the patient showed clinical and biochemical improvement. Endoscopic retrograde cholangiography was feasible and assured patent biliary anastomoses.

Conclusion

In mongrel dogs, biliary reconstruction using pedicled gastric tube interposition between CBD and duodenum is feasible with satisfactory clinical results, anastomotic circumference and histological evidence of healing. The technique is also feasible in human and seems to be promising.     

<Emphasis Type="Italic">Trichosporon inkin</Emphasis> Esophagitis: An Uncommon Disease in a Patient with Pulmonary Cancer

Trichosporon species are usually opportunistic pathogens. Here, we present a case of esophagitis caused by T. inkin in a 54-year-old woman with pulmonary cancer and severe neutropenia in whom the susceptibility profile of the isolate against azoles and polyenes was verified. The patient was diagnosed with esophagitis grade I of Wilcox, presenting scattered whitish plaques and exudates in upper two-thirds of the esophageal mucosa. Antifungal therapy involving oral fluconazole (150 mg/day for 14 days) was ineffective. In vitro, the isolate showed no resistance to this azole and sensitivity to amphotericin B. Since T. inkin is of growing importance as an agent of invasive infections in immunocompromised patients, we stress that the diagnosis of esophagitis by this species should be followed by an assessment of the therapeutic sensitivity of the strain involved.     

Human Cutaneous Protothecosis: A Case Report and Review of Cases from Mainland China,Hong Kong,and Taiwan

We present a case of cutaneous protothecosis caused by Prototheca wickerhamii infection. The patient was a 72-year-old man with hypoalbuminemia. He responded well to fluconazole treatment. We reviewed this case along with 17 other cases of cutaneous protothecosis reported from mainland China, Hong Kong, and Taiwan. Of the 18 cases, 7 each occurred in mainland China and Taiwan, and 4 occurred in Hong Kong. Thirteen cases were caused by P. wickerhamii (72.2%), and three were caused by P. zopfii (16.7%); in two cases, the species was not identified (11.1%). In all, 9 (50%) patients were immunocompromised, and 10 (55.5%) patients denied having a history of trauma. All patients presented with polymorphic skin lesions, and erythematous papules, plaques, or nodules was the most common presentation (15/18, 83.3%). Genotyping was performed in five cases, mostly by means of small subunit ribosomal DNA amplification (four cases). Susceptibility tests (6 patients) showed that P. wickerhamii was sensitive to amphotericin B and voriconazole but resistant to fluconazole or itraconazole. Treatment succeeded in 15 (83.3%) patients and failed in 3 (16.7%). Our data indicate that the number of cutaneous protothecosis cases is underestimated in China, and the skin lesions have some diagnostic value.     

Urinary tract infection caused by Hansenula anomala

A case of urinary tract infection due to Hansenula anomala is reported. The infection occurred in a cadaver kidney transplant patient who was receiving immuno-suppression therapy. Survey of the literature revealed that human infections due to this organism are rare and its causal relationship in urinary tract infection has not been previously reported.     

Functional organization of olfactory processing in the accessory lobe of the spiny lobster

An isolated brain preparation was used to characterize neurons innervating the accessory lobe (AL) of the spiny lobster (Panulirus argus). Four distinct classes of neurons responded to electrical stimulation of the olfactory (antennular) nerve. These cells responded to electrical stimulation with a long and variable latency; they also responded to odor stimulation in a nose-brain preparation. Neurons connecting the AL with the olfactory lobe branched in the central AL layer and selectively innervated olfactory lobe glomeruli. These cells had response latencies which were significantly shorter than those of other AL neurons. Intrinsic AL interneurons were heterogeneous as a population, and most arborized in irregular but circumscribed regions of either the lateral or medial layers. The final class of neurons branched ipsilaterally in the deutocerebral neuropil and bilaterally innervated only a few AL glomeruli. The physiology and morphology of these four classes of neurons confirm an olfactory function for the AL and identify the input and output regions of the lobe. Based on these findings, we propose that the AL processes odor information in the context of higher order multimodal input.Abbreviations AL accessory lobe - DCN deutocerebral neuropil - OGT olfactory-globular tract - OGTN olfactory-globular tract neuropil - OL olfactory lobe     

Muscular-skeletal cryptococcosis in a patient with idiopathic CD4+ lymphopenia

A healthy 27-year-old woman presented, four months after childbirth, ingravescent pain and claudication of the left lower limb. Magnetic Resonance Imaging of the lumbosacral and iliac regions showed widespread muscular-skeletal lesions. The patient underwent surgery; Cryptococcus neoformans was isolated from surgical samples. Liposomal amphotericin B, fluconazole and itraconazole were administered. Laboratory findings showed lymphocytopenia, with reduction of CD4+ lymphocytes (23 cells per cubic millimeter) in the absence of HIV infection and any other defined immunodeficiency. This is a rare case of muscular-skeletal cryptococcal infection isolated in a subject affected with idiopathic CD4+ lymphocytopenia. This revised version was published online in June 2006 with corrections to the Cover Date.     

Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma

Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs. Twenty-seven hypermethylated and 13 hypomethylated potential promoter regions of microRNAs, known to be associated with cancer-related pathways like Wnt, ErbB, and PI3K-Akt signaling, were identified. Selected DMRs were confirmed in 2 independent patient cohorts. Inverse correlation between promoter methylation and expression suggested miR-129-2 and members of the miR-200 family (miR-200a, miR-200b, and miR-429) as novel tumor suppressors and oncomiRs, respectively, in CC. Tumor suppressor genes deleted in liver cancer 1 (DLC1), F-box/WD-repeat-containing protein 7 (FBXW7), and cadherin-6 (CDH6) were identified as presumed targets in CC. Tissue microarrays of a representative and well-characterized cohort of biliary tract cancers (n=212) displayed stepwise downregulation of CDH6 and association with poor patient outcome. Ectopic expression of CDH6 on the other hand, delayed growth in the CC cell lines EGI-1 and TFK-1, together suggesting a tumor suppressive function of CDH6. Our work represents a valuable repository for the study of epigenetically altered miRNAs in cholangiocarcinogenesis and novel putative, CC-related tumor suppressive miRNAs and oncomiRs.     

MicroRNA和自噬参与胆管癌发病机制的研究进展

胆管癌是一种高度转移的恶性肿瘤,包括肝内胆管癌和肝外胆管癌,目前手术被认为是唯一的根治方案。胆管癌在全球的发病率和死亡率不断增加,原因很可能与早期胆管癌没有明显的临床表现,确诊时通常已达晚期阶段,及预后差、极易复发的特点有关。与人类胆管癌相关的microRNAs有很多,调节着胆管肿瘤的发生发展。此外,自噬作为细胞内环境的一种调节机制,也调节肿瘤恶变和癌症进展,在不同情况下治疗性干预,促进或抑制自噬将有利于胆管癌患者。现将microRNA和自噬参与胆管癌发生发展作一综述。     

Deep dermatophytoses in association with atopy anddiabetes mellitus: Majocchi's granuloma tricophyticum ordermatophytic pseudomycetoma?

Two patients presenting with subcutaneous nodules, plaques, papules and ulceration caused by dermatophytes are described in this report. The first case was atopic and had used low dosesystemic corticosteroids intermittently for his asthma. The second case was a poorly controlled and long-standing diabetic patient. The diagnoses were suspected after direct microscopical examinations of the discharge materials which revealed the presence of hyaline hyphae and spores, and histological examination which showed an inflammatory infiltrate with fungal elements in the dermis. Cultures of puncture materials and skin biopsies confirmed the diagnosis identifyingTrichophyton rubrumand T. mentagrophytes var interdigitale,in the first and second case respectively. Antifungal therapy with itraconazole was successful in both patients. The cases are presented to emphasize the possibility of this unusual condition in association with atopy and diabetes mellitus as in profoundly immunosuppressed cases. The nomenclature concerning this type of dermatophyte infections is also discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Identification of three classes of multiglomerular,broad-spectrum neurons in the crayfish olfactory midbrain by correlated patterns of electrical activity and dendritic arborization

We recorded electrical activity from three different classes of broad-spectrum, multiglomerular neurons in the crayfish (Procambarus clarkii, P. blandingi) olfactory midbrain. Responses were obtained to odorants and electrical stimuli applied to the antennules of isolated, perfused head preparations. All three neuronal types responded to a complex mixture of five amino acids as well as to solutions of a commercial fish food. At least two classes also responded to individual amino acids and to sugars. The response properties and the morphologies of the neurons were unique to each type. Responses of Type I cells were stimulus-dependent excitatory postsynaptic potentials and superimposed impulse trains; those in Type II were stimulus-dependent inhibitory postsynaptic potentials; those in Type III were compound responses consisting of short latency hyperpolarizations, followed by depolarizing post-synaptic potentials and impulses. All three cell types had extensive, multiglomerular dendritic arbors in the olfactory lobe, but each of their respective branching pattern morphologies was distinctive. Two types had additional dendrite branches in the lateral antennular neuropil and the olfactory-globular tract neuropil. We conclude that these broad-spectrum neurons are part of a parallel olfactory pathway that is separate from the putative quality coding circuitry in the crayfish olfactory system.Abbreviations AL accessory lobe - LAN lateral antennular neuropil - OGT olfactory globular tract - OGTN olfactory globular tract neuropil - OL olfactory lobe     

Disseminated <Emphasis Type="Italic">Penicillium Marneffei</Emphasis> Infection in an SLE Patient: A Case Report and Literature Review

Penicillium marneffei is an important opportunistic pathogen in Southeast Asia in HIV-positive individuals, but it rarely infects non-HIV ones. Four SLE patients with disseminated penicilliosis had been previously reported out of which 3 died. We describe a 46-year-old Chinese woman who had a 10 years history of SLE, associated with disseminated Penicillium marneffei infection, which presented as fever, subcutaneous masses, and fine nodular shadows disseminated over lung fields. She was initially misdiagnosed as miliary tuberculosis and panniculitis that did not respond to anti-tubercular drugs and prednisone. The correct diagnosis was finally made by histopathology and tissue culture and also culture from exudate. She responded well to antifungal therapy in the form of intravenous amphotericin B for 2 weeks followed by itraconazole plus fluconazole. The cutaneous lesions were cured leaving behind scars by secondary suture after times of epluchage, and the fine nodular shadows over lungs disappeared finally. She had no recurrence on 8 months of follow-up. We also review the literature on this topic.