scholarly journals SDHA Germline Variants in Adult Patients With SDHA-Mutant Gastrointestinal Stromal Tumor

2022 ◽  
Vol 11 ◽  
Author(s):  
Maria A. Pantaleo ◽  
Milena Urbini ◽  
Angela Schipani ◽  
Margherita Nannini ◽  
Valentina Indio ◽  
...  
Keyword(s):  
Clinical Course ◽  
Familial Cancer ◽  
Wild Type ◽  
Cancer History ◽  
Germline Variants ◽  
Older Adulthood ◽  
Stromal Tumors ◽  
Splicing Variants ◽  
The Mean

BackgroundSDH-deficient gastrointestinal stromal tumors (GIST) account for 20–40% of all KIT/PDGFRA-negative GIST and are due to mutations in one of the four SDH-complex subunits, with SDHA mutations as the most frequent. Here we sought to evaluate the presence and prevalence of SDHA variants in the germline lineage in a population of SDHA-deficient GIST.MethodsGermline SDHA status was assessed by Sanger sequencing on a series of 14 patients with gastric SDHA-deficient GIST.ResultsAll patients carried a germline SDHA pathogenic variant, ranging from truncating, missense, or splicing variants. The second hit was the loss of the wild-type allele or an additional somatic mutation. One-third of the patients were over 50 years old. GIST was the only disease presentation in all cases except one, with no personal or familial cancer history. Seven metastatic cases received a multimodal treatment integrating surgery, loco-regional and medical therapy. The mean follow-up time was of 10 years, confirming the indolent clinical course of the disease.ConclusionSDHA germline variants are highly frequent in SDHA-deficient GIST, and the disease may occur also in older adulthood. Genetic testing and surveillance of SDHA-mutation carriers and relatives should be performed.

scholarly journals Reduced Clinical Efficacy of Pazufloxacin against Gonorrhea Due to High Prevalence of Quinolone-Resistant Isolates with the GyrA Mutation

1998 ◽  
Vol 42 (3) ◽  
pp. 579-582 ◽  
Author(s):  
Masatoshi Tanaka ◽  
Tetsuro Matsumoto ◽  
Misao Sakumoto ◽  
Koichi Takahashi ◽  
Takeshi Saika ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Oral Dosage ◽  
Antibiotic Susceptibility Testing ◽  
Wild Type ◽  
Gonococcal Urethritis ◽  
Negative Culture ◽  
High Prevalence ◽  
The Mean ◽  
Gyra Mutation

ABSTRACT Forty-two men with gonococcal urethritis were treated with an oral dosage of 200 mg of pazufloxacin, a new fluoroquinolone, three times daily for 3 days. Only 28 of the 42 men (66.7%) had negative culture results for Neisseria gonorrhoeae during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic susceptibility testing and DNA sequencing. In 26 of the 41 isolates (63.4%), GyrA mutations with or without ParC mutations were identified. Among the 26 isolates, 23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2 contained three mutations including double GyrA and single ParC mutations. A single Ser-91-to-Phe mutation, which was detected in 14 of the 26 isolates, was the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp-95 to Asn or Gly mutation in GyrA. All three isolates with two or three mutations contained the Ser-91-to-Phe GyrA mutation. Eleven of the 14 isolates with the single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three mutations persisted after pazufloxacin treatment. On the other hand, all 15 wild-type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were eradicated. The mean MIC of pazufloxacin for mutants with the single Ser-91-to-Phe mutation in GyrA was 66-fold higher than that for the wild type. The results obtained in this study suggest that a high prevalence of fluoroquinolone-resistant gonococcal isolates with the Ser-91-to-Phe mutation in GyrA reduced the efficacy of pazufloxacin as treatment for gonococcal urethritis.

Fibromuscular Dysplasia of the Internal Carotid Artery

Neurosurgery ◽  
1982 ◽  
Vol 10 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Ralph P. Wells ◽  
Robert R. Smith
Keyword(s):  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Medical Records ◽  
Fibromuscular Dysplasia ◽  
Internal Carotid ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Specific Therapy ◽  
The Mean

Abstract The natural course of fibromuscular dysplasia (FMD) of the internal carotid artery (ICA). a stenosing angiopathy associated with cerebrovascular insufficiency, has not been described. A search of medical records located 16 female patients with angiographically demonstrated FMD of the ICA. The identical twin of 1 patient was included in the registry on the basis of noninvasive studies consistent with FMD of the ICA. The mean age at diagnosis was 58 years. Follow-up examinations were performed an average of 3.8 years after diagnosis (range, 1 to 9 years); the evaluation included clinical, angiographic, and Doppler studies. Fifteen patients showed no evidence of progression of FMD, whereas 2 patients with coincident atherosclerotic disease had suffered strokes. One patient had undergone surgical dilatation of the ICA. 3 had received oral anticoagulants, and 13 had received either aspirin or no specific therapy. In light of the apparently benign clinical course of uncomplicated FMD of the ICA, it is concluded that dilatation is rarely warranted.

Hemangiopericytoma of the Nasal Cavity: A Review of 15 Cases over a 40-Year Period

1992 ◽  
Vol 6 (6) ◽  
pp. 203-209 ◽  
Author(s):  
Kenneth V. Hughes ◽  
Michael C. Bard ◽  
Jean E. Lewis ◽  
Jan L. Kasperbauer ◽  
George W. Facer
Keyword(s):  
Local Recurrence ◽  
Nasal Cavity ◽  
Paranasal Sinuses ◽  
Clinical Course ◽  
Recurrence Rates ◽  
Long Term Follow Up ◽  
Vascular Origin ◽  
The Mean

Hemangiopericytomas are rare tumors of vascular origin most commonly found in the extremities or retroperitoneal area. When they originate from the nasal cavity and paranasal sinuses, they tend to be less aggressive and generally do not metastasize. The term “hemangiopericytoma-like lesion” has been coined for sinonasal hemangiopericytomas that display more benign histologic and growth characteristics than do those located elsewhere. Fifteen cases of hemangiopericytoma of the nasal cavity and paranasal sinuses were reviewed over the period 1951 to 1990; included are follow-up data on cases reported earlier from this institution. The clinical course, management, and outcome was evaluated and correlated with the histologic characteristics of the tumors. The recurrence rate in our series was 13.3%; the mean follow-up was 11 years. No patients died of their disease or had evidence of metastatic disease. This clinicopathologic review suggests that sinonasal hemangiopericytomas should not be classified as “hemangiopericytoma-like” lesions; rather, they should be expected to have significant local recurrence rates with low rates of distant metastasis and mortality. Long-term follow-up is essential as there can be local recurrence after many years.

scholarly journals Predictors and Conversion Rate of Clinically Isolated Syndrome to Clinically Definite Multiple Sclerosis: A Follow-up Study in Patients Living in the Southern Part of Iran

2020 ◽  
Vol 6 (1) ◽  
pp. 9-15
Author(s):  
Sadegh Izadi ◽  
◽  
Meysam Ahmadi ◽  
Maryam Poursadeghfard ◽  
◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Conversion Rate ◽  
Regression Models ◽  
Cox Regression ◽  
Clinical Course ◽  
Clinically Isolated Syndrome ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
The Mean

Background: Clinical course of Clinically Isolated Syndrome (CIS) is variable, and identifying patients who will eventually develop Multiple Sclerosis (MS) is essential. Objectives: To assess the conversion rate of CIS to Clinically Definite Multiple Sclerosis (CDMS) and its predictors in southern Iran. Materials & Methods: A total of 143 CIS patients registered to Fars Multiple Sclerosis Society (FMSS) were enrolled in the study from 2006 until 2012, and all of them were followed for 5 years. Also, their demographic and MRI data were recorded. The obtained data were analyzed by univariate and multivariable Cox regression models in SPSS v. 17. P<0.05 was considered statistically significant. Results: About 26.6% of patients progressed to MS after a mean duration of 3.4±1.1 years. The conversion rate was 27.6% in patients presented with optic neuritis, and 25.6% in patients presented with spinal cord problems. Although it was not statistically significant (P=0.23), the mean age of the patients who converted to MS was lower at the onset of the presentation (27.6 vs. 29.4 years). In patients who had 3 or more MRI lesions, the conversion rate was 49.2%; however, it was only 9.8% in subjects who had fewer than 3 lesions (OR=8.95, 95% CI=3.69–21.7, P <0.001). Women had higher conversion rate though it was not statistically significant (OR=2.09, 95% CI=0.57–7.64, P=0.26). Conclusion: Our results supported this supposition that the number of MRI lesions at baseline can be used as a predictor of CIS conversion to MS.

scholarly journals Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm

2018 ◽  
Vol 44 (6) ◽  
pp. E15 ◽  
Author(s):  
Malte Mohme ◽  
Friederike S. Fritzsche ◽  
Klaus C. Mende ◽  
Jakob Matschke ◽  
Ulrike Löbel ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Course ◽  
Case Series ◽  
Diffuse Astrocytoma ◽  
The Mean ◽  
Mean Time ◽  
Tectal Glioma ◽  
Astrocytoma Grade

OBJECTIVETectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology.METHODSClinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients.RESULTSThe patients’ mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts.CONCLUSIONSAnalysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

252. Morphometric and histological analysis of ovaries from sheep heterozygous for the prolific woodlands allele

2005 ◽  
Vol 17 (9) ◽  
pp. 101
Author(s):  
E. S. Feary ◽  
J. L. Juengel ◽  
P. Smith ◽  
A. R. O'Connell ◽  
G. H. Davis ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Follicular Development ◽  
Wild Type ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Mechanistic Pathway ◽  
Morphometric Methods ◽  
The Mean ◽  
Large Ovary

Woodlands are a line of Coopworth sheep with a novel, imprinted X-linked fecundity allele resulting in ovulation rates about 0.40 higher than wild-type animals. Daughters of progeny tested sires with and without the gene were studied. Previously, lambs heterozygous for the Woodlands allele were found to have larger ovaries and more antral (i.e. type 5) but not preantral (i.e. types 1–4) follicles than in wild-type contemporaries. The large ovary phenotype was found to be transient and was absent after puberty. However, based on follow-up studies it was evident that the large ovary phenotype was not strongly associated with the Woodlands fecundity allele. Thus, it was uncertain whether animals carrying the Woodlands gene had different follicular populations compared to wild-type controls. To address this question, follicular populations were compared in adult ewes heterozygous for the Woodlands allele with age-matched controls. Using standard morphometric methods and histological analysis, no differences were observed in the mean numbers of types 1, 1a, 2, 3 and 4 preantral follicles between the genotypes. Furthermore, no differences were observed between genotypes in follicular or oocyte diameters for any follicular type. The adult Woodlands carrier ewes had twice as many small type 5 follicles (< 1mm) when compared to wild-type contemporaries although no difference was seen in the numbers of antral follicles > 1mm in diameter. In addition, antrum formation occurred at a smaller follicular diameter in the heterozygous Woodlands animals. Therefore, the increased number of antral follicles observed in both lambs and adult ewes suggests that this difference in pattern of follicular development is associated with the X-linked fecundity allele. This novel phenotype of early antrum formation and larger number of small preantral follicles differs from that observed in sheep with the Inverdale or Booroola mutations, suggesting that a different mechanistic pathway is involved. Acknowledgements: The Marsden Fund, FRST and Ovita.

A multi-institutional investigation assessing prevalence of germline genetic alterations in Chinese patients with gastric carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13020-e13020
Author(s):  
Yinjie Zhang ◽  
Xicheng Wang ◽  
Changbin Zhu ◽  
Xiaotian Zhang ◽  
Qing Wei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Family History ◽  
Gastric Carcinoma ◽  
Familial Cancer ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Multiple Primary Cancers ◽  
Cancer History ◽  
Germline Variants

e13020 Background: Gastric carcinoma is one of the most common malignancies in east asian. Previous studies demonstrated around 10% of patients with gastric cancer were found to have pathogenic germline variants. While, predisposition genes of gastric cancer in Chinese patients are still largely unknown. Thus, we aim to delineate prevalence of deleterious germline mutations in Chinese gastric patients with hereditary high-risk familial cancer history. We also aim to analyze clinical relevance of deleterious germline mutations. Methods: Forty index cases were recruited from 7 institutions in China. DNA samples extracted from blood specimens were captured using a 171-cancer predisposition gene panel and then sequenced by MGI-SEQ 2000 platform. Germline variants were determined to be deleterious according to the ACMG 2015 guidelines. Pathogenic and Likely pathogenic germline variants were further validated by Sanger sequencing. Results: 12 of 40 (30%) probands had 13 pathogenic/likely pathogenic germline variants involving 11 different genes: CHEK2 (n = 2), SPINK1 (n = 2), BLM (n = 1), CDH1(n = 1), EXT2 (n = 1), MLH1 (n = 1), MSH2(n = 1), MUTYH (n = 1), PALB2 (n = 1), NF1 (n = 1), ERCC2 (n = 1). For patients with multiple primary cancers, pathogenic germline alterations were exclusively presented (5 out of 12) (P=0.003). Besides,27 germline variants (like EPCAM, RAD54B, FANCD2, FANCA) with uncertain significance in 15 patients were predicated to be deleterious via in silico predictors. Conclusions: This multi-institutional study identified 30% (12/40) of Chinese gastric cancer patients with family history to have deleterious germline alterations. And potential deleterious variants were also identified. Our data illustrates a significantly distinguished spectrum of germline variants compared with Caucasian ones. This may indicate unique carcinogenesis of gastric cancer in Chinese patients. Since patients with pathogenic or likely pathogenic germline variants have dismal clinical outcome and higher rate of multi-cancer occurrence, genetic counseling of gastric cancer should be considered for individuals with family history at their early age.

Extracapillary Proliferative Glomerulonephritis in Children

PEDIATRICS ◽  
1975 ◽  
Vol 56 (3) ◽  
pp. 434-442
Author(s):  
Sudhir K. Anand ◽  
Carl W. Trygstad ◽  
Hari M. Sharma ◽  
James D. Northway
Keyword(s):  
Streptococcal Infection ◽  
Clinical Course ◽  
Renal Involvement ◽  
Therapeutic Agents ◽  
Proliferative Glomerulonephritis ◽  
The Mean ◽  
Histopathologic Changes ◽  
Better Than

The clinical course and renal pathology of 17 children with acute extracapillary proliferative glomerulonephritis is reported. Patients with systemic ses associated with renal involvement were excluded. The onset followed streptococcal infection in ten; of these, four have died, one has been transplanted, and the remaining five have completely healed. The mean follow-up of the latter five patients was 32 months (range, 18 to 57 months). Of the other seven patients without evidence of preceding streptococcal infection, two have died, two have been transplanted, and the remaining three all have hypertension, proteinuria, and reduced creatinine clearance. The mean follow-up of the latter three patients was 29 months (range, 14 to 38 months). The initial renal histopathologic changes and their progress in later renal biopsies is described. The role of various therapeutic agents is discussed. The prognosis in acute extracapillary proliferative glomerulonephritis following streptococcal infection appears to be better than in ones without preceding streptococcal infection.

Abstract P057: The Association Of Diabetes Duration With Central Artery Stiffness And Its 5-year Change Among Older Adults: The Atherosclerosis Risk In Communities Study (ARIC).

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Meera Marji ◽  
Gerardo M Heiss ◽  
James R Pike ◽  
Priya Palta ◽  
Michelle Meyer ◽  
...  
Keyword(s):  
Older Adults ◽  
Arterial Stiffness ◽  
Diabetes Duration ◽  
Older Adulthood ◽  
Duration Of Diabetes ◽  
Central Artery ◽  
Rate Of Progression ◽  
Artery Stiffness ◽  
The Mean

Background: Central artery stiffness is a predictor of cardiovascular risk and mortality among individuals with diabetes. Few studies examined whether the duration of diabetes relates to arterial stiffening and its rate of progression. Objective: To examine the association of diabetes duration from midlife to older adulthood with arterial stiffness and its 5-year change. Methods: Diabetes (defined by fasting glycemia level >126 mg/dl or use of glucose lowering agents or self-reported) was ascertained at visit 1 (1988-1990), on repeated examinations and on telephone follow-up calls of 2,155 ARIC cohort members (58% women, 20% black, mean age 74 years), as well as time since ascertainment of diabetes. Carotid femoral pulse wave velocity (cfPWV), a measure of central artery stiffness, was obtained at cohort visits 5 (2011-13) and 6 or 7 (2016-19). Associations of duration of diabetes with visit 5 cfPWV and the 5-year cfPWV change from visit 5 to visit 6 or 7 were evaluated by multivariable linear regression adjusted for demographic factors. Results: Among study participants with diabetes ascertained from midlife to older adulthood (n=639 (29%)), the mean cfPWV at visit 5 was 78.6, 95%CI (52.9, 104.4) cm/s greater than those without diabetes. Over a mean of 4.9 (SD 3) years of follow-up, cfPWV increased by a median 137 cm/s. The 5-year change in cfPWV was 40.5, 95%CI (12.3, 68.8) cm/s greater among those with diabetes, as compared to those without diabetes. The mean diabetes duration was 8.1(SD 6.8) years for participants with diabetes. After adjusting for demographic factors, we observed a positive association of diabetes duration with the 5-year change in cfPWV in older adulthood (Figure). Conclusion: Duration of diabetes was associated with a greater rate of progression of central arterial stiffness in older adults.

Evolution of GPI-Deficient Clones Predicts Clinical Course in Paroxysmal Nocturnal Haemoglobinuria.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 172-172 ◽  
Author(s):  
Stephen J. Richards ◽  
Matthew J. Cullen ◽  
Anita J. Dickinson ◽  
Claire Hall ◽  
Anita Hill ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Clinical Course ◽  
Spontaneous Remission ◽  
Red Cells ◽  
Red Cell ◽  
Clone Size ◽  
Clinical Behavior ◽  
The Mean ◽  
Pnh Clone

Abstract Flow cytometric analysis of GPI-linked antigens has had a major impact on the diagnosis of PNH. Significant numbers of patients with aplastic anemia have small PNH clones, and due to the precision in clone size measurement, reliable serial monitoring can now be undertaken although the clinical value of this is not proven. From our series of 234 PNH patients, we analysed clinical correlates between disease type and red cell and granulocyte peripheral blood clone sizes as determined by flow cytometry at presentation. For hemolytic patients (n = 99) the mean PNH clone sizes were: granulocytes 84.8%; red cells 45.3% (type III cells 33.6%). For aplastic patients (no macroscopic hemolysis) the mean clone sizes were: granulocytes 18.5%; red cells 6.4% (type III cells 4.5%). The two groups were statistically different (Mann Whitney U; P<0.001). Monitoring of PNH clones in 86 of these patients who had at least 3 samples over a minimum of 12 months (mean 55 months; range 15–174) not only showed distinct groups of patients with highly characteristic patterns of disease but also provided insights into the incidence of spontaneous remission, progression from aplastic to hemolytic disease, and development of leukemia. Firstly, hemolytic patients that present with >90% granulocyte clones (n = 30; mean follow up 48 months) with virtually all their hematopoiesis maintained from PNH stem cells have clone sizes that remain stable and their clinical behavior suggests that their PNH can persist for up to 40 years. The second group of patients (n = 16) were those with hemolytic PNH with granulocyte clones of <90%. Mean granulocyte clone size at presentation was 68.4% (range 34.7– 90%) with a mean follow-up of 66 months (range 24–164). Of these, 6 showed stable clone sizes, 2 increasing clone size, and 8 showing reductions in granulocyte clone size. The third group were those presenting with aplastic anemia (n = 34). This group showed the most significant variation in clone size and clinical behavior. Of the 12 patients with persistent aplastic anemia, the majority had slowly increasing clone sizes with 5 patients progressing to hemolytic PNH after a variable time period ranging from 26 to 79 months. Only 3 patients developed MDS or AML. Two of these were from the >90% granulocyte clone group (2/30) and developed as a terminal event, one with GPI-MDS, and the second with a rapid emergence of GPI+MDS. One patient in the aplastic group showed progression to AML (1/34). 27% of patients had an improvement in cytopenias with concurrent decrease in PNH clone size. For hemolytic patients with granulocyte clones of <90%, the 8 patients with falling clone sizes had improving blood counts. The PNH granulocyte clone halved in a mean of 74 months. Of the patients with aplastic anemia, 15 showed resolution of anemia with normalization of counts and all but one had an associated fall in granulocyte PNH clone sizes. Eleven patients have been treated in clinical trials of the anti-complement antibody, eculizumab, for a period of up to 2 years and over this period the proportion of PNH granulocytes has remained stable. This data demonstrates that the size and type of granulocyte and red cell PNH clones at presentation predicts the clinical course for individual patients assisting long term clinical management planning. Moreover, regular clone size monitoring predicts the likelihood of spontaneous reduction in the PNH clone and potentially for spontaneous remission.

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