SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The diagnosis of unstable angina may be confirmed if an ECG taken during an episode of pain demonstrates ST-segment changes that resolve when the pain is relieved. An intra-aortic balloon device should be used in the rare patient who has recurrent episodes of ischemia despite maximum drug therapy. Coronary angiography should be performed as soon as possible after the device is inserted.
Germ-line mutations of the BRCA1 gene account for approximately half of the cases of hereditary breast/ovarian cancers. We have screened index patients from 15 breast cancer families and 8 sporadic breast cancer patients from Latvia for mutations in all coding exons of the BRCA1 gene, using combined Heteroduplex Analysis/SSCP followed by direct sequencing of the variants. BRCA1 germ-line mutations proved to be frequent in Latvian breast cancer patients, also in moderate-risk families and sporadic patients. Out of 23 cases a total of 8 patients (35%) exhibited three different mutations (5382insC, C61G, 4153delA). Interestingly, these three recurrent mutations accounted for all mutations in our sample set and no unique mutation was found. The 5382insC and C61G mutations accounted for 63% (5/8) and 25% (2/8) of all mutations, respectively. Allelotyping suggested a common founder in each recurrent mutation. Additional one-hundred hospital-based incident breast cancer patients were screened for the three mutations and 4 other 5382insC mutation carriers were identified (4%). Patients with C61G and 4153delA mutations were all Latvians, whilst the majority of 5382insC carriers (7/9=78%) were of Russian ethnicity, which is intriguing for the supposed Baltic origin of this mutation.
Forty-four follicular thyroid neoplasms followed for a minimum of 10 years are presented. The cases were divided into four categories: follicular adenoma (19 cases), encapsulated follicular carcinoma (7 cases), invasive follicular carcinoma (11 cases), and the follicular variant of papillary carcinoma (7 cases). The former two tumor types were distinguished by the presence of capsular invasion in encapsulated follicular carcinoma (which was defined as lacking extension into the surrounding thyroid) and by the frequent thinness of the capsule in follicular adenoma, while the latter two (which both infiltrated adjacent thyroid or extrathyroid tissue) were separated primarily on the basis of the tendency toward vesicular and hypochromatic nuclear staining in the follicular variant of papillary carcinoma, but with consideration of a number of other factors in addition. No patient with follicular adenoma had any further difficulty after removal of the lesion. Metastasis to cervical lymph nodes occurred in five cases of the follicular variant of papillary carcinoma, but there were no distant metastases or deaths due to tumor. By contrast, three patients with encapsulated follicular carcinoma and nine with invasive follicular carcinoma died of tumor, and all of these had distant metastasis (most often to bone). Local recurrence was seen only in invasive follicular carcinoma (six cases).
PURPOSE: To report a case of mucoepidermoid carcinoma, a highly aggressive variant of conjunctival squamous cell carcinoma. METHODS: We examined and treated a 57-year-old man with mucoepidermoid carcinoma of the caruncle, a highly unusual site for this tumor. RESULTS: In the past, simple excision of this tumor has been followed by rapid recurrence. Our patient underwent wide surgical excision of the tumor and has shown no evidence of recurrence after 16 months of follow-up. CONCLUSION: Mucoepidermoid carcinoma may first manifest in the caruncle. Histologically verified, tumor-free surgical margins are necessary for complete excision.
Recent epidemiological research in the general population and primary care demonstrated that a substantial proportion of disabling depressive syndromes do not meet the diagnostic criteria for major depression. This observation proposes less restrictive diagnostic definitions of depression. However, a gain in sensitivity may induce a substantial loss of specificity. A variety of diagnostic definitions of subthreshold depression has been proposed balancing both aspects. However, the less restrictive diagnostic definitions are, the lower the specificity. This report explores variants of subthreshold depression characterized by current and subsequent disability in a prospectively investigated sample of general practice patients (n = 400), recruited within the framework of the WHO study "Psychological Problems in Primary Care and a survey in the general population. Duration of episodes, recurrence and number of associated symptoms are the main diagnostic variables. Brief depression with multiple episodes per year (including recurrent brief depression as defined by ICD-10) is comparable to major depression by social disability and subsequent course in the sample under study.
BACKGROUND/AIMS: The success of treatment with hepatitis B hyperimmune globulin in preventing recurrence of hepatitis B virus infection in patients undergoing orthotopic liver transplantation depends on maintaining levels of anti-HBs sufficient to neutralise hepatitis B virus and also on patient compliance. Breakthrough infections may occur, and these have been associated with the emergence of variants in HBsAg. METHODS: Three patients, two who relapsed and one who had no evidence of hepatitis B virus infection post-orthotopic liver transplantation were studied. Polymerase chain reaction and sequencing of pre- and post-orthotopic liver transplantation samples was followed by antigenic analysis of the in vitro expressed cloned sequences. RESULTS: In two patients who were treated with hyperimmune globulin, amino acid variation in the region of the immunodominant B cell epitopes of HBsAg occurred. Sequencing of clones revealed fluctuating variant sequences over time. One had clinical relapse and immune escape was evident on in vitro antigenic analysis. Patient two lost HBsAg reactivity post-orthotopic liver transplantation. There was loss of an antigenically critical cysteine molecule; sequencing of clones revealed that this was the dominant species. The third patient relapsed when protective levels of anti-HBs were not maintained; HBsAg showed no variation compared to a standard subtype sequence. CONCLUSION: These data provide strong experimental evidence of immune escape. It appears that hyperimmune globulin provides the selection pressure. In these patients, HBsAg negativity does not exclude infection of the transplanted liver.
Over the past years, a number of idiopathic, chronic, inflammatory gastrointestinal diseases have been recognized, which can be distinguished from Crohn's disease and ulcerative colitis. These entities are grouped under the term "variant forms" of IBD. In this review, three distinctive, variant-IBD entities--all of which with individual and uniform histories and characteristic, histological abnormalities, but unremarkable or even absent endoscopical features--are presented: 1. The adult form of primary eosinophilic esophagitis mainly affects male patients and leads to a history of acute and recurrent dysphagia with a typical on-off-phenomenon. 2. Patients with celiac disease often present a long history of anemia and complain of symptoms resembling irritable bowel syndrome. 3. The main symptom of microscopic colitis is watery diarrhea, sometimes associated with weight loss. Faced with one of these histories, it is necessary to insist, that during the endoscopic procedures--even in the absence of mucosal alterations--representative biopsy specimens are taken and histologically worked up with adequate stainings.
In non-smokers the underlying causes for chronic persistent cough (CPC) e.g. chronic cough without diagnostic chest X-ray or pulmonary function test--are usually as follows: several common upper airways diseases, bronchial (cough type) asthma, gastrooesophageal reflux or treatment with an ACE (angiotensin converting enzyme)--inhibitor. In 10% of CPC however the cause remains uncertain. We report a 30 year old non-smoker with severe coughing and repeated vomiting for two months. No laboratory or technical data could be collected suggestive of a common cause of CPC: Upper airways disease, bronchial flow limitation or hyperresponsiveness, ACE inhibitor medication, B. pertussis infection, gastrooesophageal reflux disease (by 24 hours pH-probe) were ruled out. Fiberbronchoscopic findings remained unremarkable, except for the bronchial biopsy specimen, which showed moderate eosinophilic inflammation of the mucosa and marked thickening of the subepithelial layer. Since the cough was non-productive, sputum induction with 3 ml nebulised 3% NaCl solution was performed. 28% of the granulocytes were eosinophil stained. A low quality morning sputum (< 1 ml) showed 21% eosinophilia. Thus, the diagnosis of eosinophilic bronchitis was established. 400 micrograms budesonide dry powder inhalations b.i.d. for one week resolved the cough, treatment was stopped after three weeks. No recurrence was seen two months later. Both the cough type asthma and the eosinophilic bronchitis could represent a form fruste of classical bronchial asthma beyond wheezing or dyspnoea, but with the common main symptom: cough. Since hyperresponsiveness and cough are phenotypic hallmarks of cough variant asthma, in eosinophilic bronchitis--beside cough--another two features of asthma are present: eosinophilic inflammation of the mucosa along with sputum eosinophilia and subepithelial layer thickening. Not surprisingly, eosinophilic bronchial inflammation could be shown in patients with cough variant asthma as well, who--up to 56% during a four year-period--develop classic asthma. The long-term outcome of eosinophilic bronchitis is not known, however. Thus, asthma, cough variant asthma and cough due to eosinophilic bronchitis can mirror different phenotypes or phases of the same entity. CPC due to either the cough type asthma or the eosinophilic bronchitis is like asthma fast responding to inhalative steroids. (Induced) sputum staining should be added to the diagnostic armamentarium of CPC.
Because tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells and plays a critical role in tumor surveillance, its receptor is an attractive target for antibody-mediated tumor therapy. Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor-expressing innate immune cells, with no apparent systemic toxicity. Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases. Notably, the anti-DR5 mAb-mediated tumor rejection by innate immune cells efficiently evoked tumor-specific T cell immunity that could also eradicate TRAIL-resistant variants. These results suggested that the antibody-based therapy targeting DR5 is an efficient strategy not only to eliminate TRAIL-sensitive tumor cells, but also to induce tumor-specific T cell memory that affords a long-term protection from tumor recurrence.
The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T-->C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T-->C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.
Eighteen examples of an unusual malignant soft-tissue neoplasm, the morphology of which ranged from that of "atypical" epithelioid sarcoma to that of a rhabdoid tumor or undifferentiated carcinoma (with transitional forms) are described. Patients included 11 males and seven females; their median age was 35.5 years with most patients aged 20 to 40 years. Development of a mass was the main presenting symptom. Six tumors developed in the pelvis and perineal region, four in the pubic region and vulva, three in the buttocks, one in the deep soft tissues of the left hip, one on the penis, one in left forearm, one in left axilla, and one on the occiput. Tumor size ranged from 1 to 20 cm (median, 4 cm). On microscopic examination, the tumor cells invaded the subcutaneous or deep soft tissues, had prominent epithelioid or rhabdoid features, had marked cytologic atypia, and grew in a multinodular pattern in half of the cases. Areas of necrosis were often seen. A granuloma-like pattern reminiscent of that observed in classic epithelioid sarcoma was observed in only two cases. Immunohistochemically, positivity for cytokeratin, epithelial membrane antigen, and vimentin was seen in all but one of the cases. Of 16 cases, 10 and eight tumors reacted with desmin and CD34, respectively; five of 15 reacted at least focally with smooth-muscle actin, whereas three of 13 and one of 10 reacted for HMB-45 and carcinoembryonic antigen, respectively. S-100 protein and CD31 yielded negative results. Seven tumors were investigated at the ultrastructural level, four of which showed prominent intracytoplasmic intermediate filament aggregates, often accumulating into paranuclear whorls, which is in keeping with the rhabdoid phenotype. Five tumors showed features of epithelial differentiation (i.e., tonofilament-like structures or desmosomes or both), whereas one tumor displayed features of myofibroblastic differentiation. Differential diagnoses include mainly conventional epithelioid sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma. Follow-up information on 14 patients (range, 4 months to 8 years; median, 19 months) revealed local recurrence in one case and metastatic dissemination in six patients, leading to death in five. In our opinion, the above-described neoplasms represent a usually "proximal-type" of epithelioid sarcoma. In contrast to the conventional, "distal-type" epithelioid sarcoma, the proximal variant is characterized by a predominantly large-cell, epithelioid cytomorphology, marked cytologic atypia, frequent occurrence of rhabdoid features, and lack of a granuloma-like pattern in most cases. It appears to be somewhat more aggressive (or at least metastasizes earlier) than usual epithelioid sarcoma.
The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multisystemic manifestations. We present 4 cases with arterial symptoms typical of acute arterial obliteration (AAO) and review 9 similar cases in the literature. The clinical course of AAO was unusual and particularly severe when affecting the lower limbs; recurrent events required amputations. As demonstrated by angiographic and histologic studies, thrombotic and atheromatous lesions were the main pathologic features of AAO. Atherosclerotic risk factors were absent or moderate in 3 of our cases, and no cause of thrombosis other than the POEMS syndrome was found. A high production of cytokines was found in all cases, with elevated serum levels of interleukin-1 beta (9/9 samples), interleukin-6 (7/9 samples), and tumor necrosis factor-alpha (6/9 samples). We suggest that arterial manifestations should be added to the spectrum of manifestations of the POEMS syndrome. Cytokines may mediate the POEMS syndrome-associated AAO, as previously proposed for the other systemic manifestations of this disorder.
Two adult cases of a cutaneous lesion indistinguishable from typical infantile digital fibromatosis are added to the unique similar case so far reported in adulthood. The immunocytochemical localization of vimentin and muscle actin in the proliferating cells confirms their myofibroblastic nature and establishes closer relationships between the adult and the infantile variants of this entity. These two variants, however, appear to be clinically different, since all the adult cases were extradigital and did not recur after surgical excision. The term inclusion body fibromatosis underlines the histological hallmark of the lesion and should be used to identify this entity in place of recurrent infantile digital fibromatosis which does not seem any longer appropriate.
A rare variant of dedifferentiated chondrosarcoma with malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhabdomyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.
PURPOSE: The matrix metalloproteinases (MMP) are a family of enzymes that can degrade extracellular matrix and facilitate invasion through the basement membrane. Several polymorphisms in MMP-1, MMP-2, MMP-3, and MMP-12 have been described, some of which lead to differential transcription. We hypothesized that polymorphisms in these MMP genes may be associated with survival outcomes in early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We evaluated the relationship between MMP-1, MMP-2, MMP-3, and MMP-12 polymorphisms and both recurrence-free survival (RFS) and overall survival (OS) among 382 patients with stage I NSCLC. Analyses of genotype associations with survival outcomes were done using Cox proportional hazards models and Kaplan-Meier methods and the log-rank test. RESULTS: Patients carrying the variant G allele of the MMP-12 1082A/G polymorphism had significantly worse outcomes [crude hazard ratio (HR) for OS 1.74; 95% confidence interval (95% CI), 1.18-2.58, P=0.006; crude HR for RFS, 1.53; 95% CI, 1.05-2.23, P=0.03]. After adjusting for age, sex, stage, pack-years of smoking, and histologic subtype, the MMP-12 1082A/G polymorphism remained significantly associated with survival outcomes [adjusted HR (AHR) for OS, 1.94; 95% CI, 1.28-2.97, P=0.002; AHR for RFS, 1.61; 95% CI, 1.07-2.41, P=0.02]. None of the other MMP polymorphisms was significantly associated with survival. CONCLUSIONS: Our results show that patients with stage I NSCLC carrying the variant G allele of the MMP-12 1082A/G polymorphism have worse survival.
BACKGROUND: Spermatogenic failure is one of the leading causes of male infertility and its genetic etiology has not yet been fully understood. METHODS: The study screened a cohort of patients (n = 167) with primary male infertility in contrast to 210 normally fertile men using whole exome sequencing (WES). The expression analysis of the candidate genes based on public single cell sequencing data was performed using the R language Seurat package. RESULTS: No pathogenic copy number variations (CNVs) related to male infertility were identified using the the GATK-gCNV tool. Accordingly, variants of 17 known causative (five X-linked and twelve autosomal) genes, including ACTRT1, ADAD2, AR, BCORL1, CFAP47, CFAP54, DNAH17, DNAH6, DNAH7, DNAH8, DNAH9, FSIP2, MSH4, SLC9C1, TDRD9, TTC21A, and WNK3, were identified in 23 patients. Variants of 12 candidate (seven X-linked and five autosomal) genes were identified, among which CHTF18, DDB1, DNAH12, FANCB, GALNT3, OPHN1, SCML2, UPF3A, and ZMYM3 had altered fertility and semen characteristics in previously described knockout mouse models, whereas MAGEC1,RBMXL3, and ZNF185 were recurrently detected in patients with male factor infertility. The human testis single cell-sequencing database reveals that CHTF18, DDB1 and MAGEC1 are preferentially expressed in spermatogonial stem cells. DNAH12 and GALNT3 are found primarily in spermatocytes and early spermatids. UPF3A is present at a high level throughout spermatogenesis except in elongating spermatids. The testicular expression profiles of these candidate genes underlie their potential roles in spermatogenesis and the pathogenesis of male infertility. CONCLUSION: WES is an effective tool in the genetic diagnosis of primary male infertility. Our findings provide useful information on precise treatment, genetic counseling, and birth defect prevention for male factor infertility.
Surgery for epithelial cancer is more and more getting a tailored surgery: wide local excision of the primary and focused retrieval of the regional lymph nodes. As far as cancer of the cervix is concerned such a strategy is avoidable: laparosopic pelvic lymphadenectomy and radical trachelectomy. This operation is a variant of the classical Schauta operation. The difference is the uterus is divided underneath the isthmus which is, at the end of the operation, stitched to the vagina. A personal series of 82 cases gathered between 1987 and 2000 is reported. The number of recurrences is three. All of them have been registered in the population of 21 patients who were affected by a cancer two cm or more large. Among the 38 patients who wanted and were able to become pregnant 29 succeeded. Among the 47 registered pregnancies 35 went on after the 14th week and 27 finished with the birth of a living baby.
The aim of this study was to evaluate the influence of suspected prognostic factors on survival in the endemic goiter area. The retrospective review of 208 consecutive patients with differentiated thyroid cancer treated at I Department of General Surgery Collegium Medicum Jagiellonian University from 1983 to 1996. In the studied population there were 98 patients (47.1%) with follicular cancer and 110 patients (52.9%) with papillary cancer. The 182 (87.5%) female and 26 (12.5%) male patients had mean age 48.8 (range from 16 to 80 years). The mean follow-up period was 11.7 years with the longest time of observation 19 years and the shortest 6 years. All the patients were living in the endemic area. Patients with differentiated thyroid cancer have very good prognoses. The 10 year survival rate in case of follicular and papillary cancer were 87.6% and 90.24% respectively. The univariate analysis identified sex, age, histological subtypes (insular and tall cells variants), extrathyroidal extension, size of the tumour beyond 70 mm, lymph node and distance metastases as well as type of surgical procedures in III stage of disease as significant prognostic factors with major effect on survival. In the multivariate analysis extrathyroidal extension, distance metastases, recurrence and lymph node metastases influenced the survival. Early detection of differentiated thyroid cancer with the help of ultrasound examination with aspiration biopsy of suspected lesions, radical surgical procedures and good histological evaluation of the removed tissues guarantee very good treatment results.
Refine your search to explore more results.