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.

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.

scholarly journals Histological study of capuchin monkey (Cebus apella) ovarian follicles

2004 ◽  
Vol 34 (3) ◽  
pp. 495-501 ◽  
Author(s):  
Sheyla Farhayldes Souza Domingues ◽  
Luiz Viana Diniz ◽  
Sonia Helena Costa Furtado ◽  
Otavio Mitio Ohashi ◽  
David Rondina ◽  
...  
Keyword(s):  
Qualitative Data ◽  
Histological Study ◽  
Follicular Development ◽  
Cebus Apella ◽  
Neotropical Primates ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
The Right

The present study aimed to obtain quanti-qualitative data about the follicular ovarian population in Cebus apella females. Seven ovaries were obtained from 4 C. apella adult females. The ovaries were subjected to light microscopy. The number of preantral and antral follicles for each ovary was estimated using the Fractionator method. The preantral follicles were classified into primordial, transitional, primary and secondary follicles. Antral follicles were those that presented an antral cavity. All counted follicles were classified as normal or degenerated. The diameter of the follicles, oocytes and their nuclei were determined to accompany the follicular development. All results were represented as mean ± SE. The number of preantral follicles was 56,938 ± 21,888 and 49,133 ± 26,896 for the right and left ovaries, respectively. The percentage of normal follicles was 80 ± 4.95%. The follicular diameter ranged from 22 ± 0.5 µm to 61.2 ± 4.0 µm. Regarding the antral follicles, the number of normal and degenerate follicles per ovary were 60.0 ± 19.0 and 3 ± 1.8 follicles, respectively. The antral follicular diameter was 514.4 + 56.6 µm. In conclusion, the information obtained in this study can be used as a parameter for subsequent in vivo or in vitro studies about folliculogenesis in non-human neotropical primates of the C. apella species.

Effect of exogenous gonadotrophins on ovarian morphology and oocyte maturation in the southern hairy nosed wombat Lasiohinus latifrons during the breeding season

2006 ◽  
Vol 18 (4) ◽  
pp. 477 ◽  
Author(s):  
C. H. McDonald ◽  
D. A. Taggart ◽  
W. G. Breed ◽  
G. V. Druery ◽  
G. A. Shimmin ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Follicular Development ◽  
Germinal Vesicle ◽  
Control Group ◽  
Antral Follicles ◽  
Nuclear Maturation ◽  
Significant Difference ◽  
Ovarian Morphology ◽  
The Mean ◽  
The Right

The effect of the exogenous administration of porcine follicle-stimulating hormone (pFSH) and pregnant mare serum gonadotrophin (PMSG) on ovarian follicular development and oocyte maturation in the southern hairy nosed wombat Lasiorhinus latifrons was investigated. Three experimental groups were administered pFSH at various doses and for different treatment lengths, followed by 25 mg porcine luteinising hormone (pLH) 12 h after the last dose of pFSH. Another group was given PMSG followed 72 h later by 25 mg pLH. Animals were killed 24 h after pLH. The left ovary was fixed for histology and the morphology of the antral follicles was determined, whereas follicular oocytes in the right ovary were aspirated, fixed, stained with 4′,6′-diamidino-2-phenylindole, and viewed for nuclear maturation. There was no significant difference in the mean number of ovarian follicles >1 mm, or in the size class of follicles assessed between control and experimental groups. However, a trend was observed suggesting a possible increase in follicles >3.0 mm in experimental groups compared with control animals. In all females administered exogenous porcine gonadotrophins, but not controls, some of the mural granulosa cells of large tertiary antral follicles had markedly enlarged nuclei (approximately 14 µm in diameter). All oocytes from the control group remained at the germinal vesicle stage, whereas approximately 40% of oocytes retrieved from the pFSH groups and 82.4% retrieved from the PMSG-primed animals had undergone germinal vesicle break down, with a small number reaching meiosis II. The present study shows that exogenous administration of either pFSH or PMSG to hairy nosed wombats can induce follicular growth and oocyte maturation. Such findings could be useful in the development of reproductive technology in this species.

scholarly journals CPX-351 for Acute Myeloid Leukaemia: Real World Results Are Comparable to Trial Outcomes and Exceeds Them in Non-Adverse Risk Patients- a Multicentre Experience from West Midlands Hospitals on Behalf of West Midlands Research Consortium ( WMRC) UK

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4416-4416
Author(s):  
Vidhya Murthy ◽  
Richard Whitmill ◽  
Clare Lodwick ◽  
Peter Dyer ◽  
Maria Ahmed ◽  
...  
Keyword(s):  
Median Survival ◽  
Real World ◽  
Remission Rate ◽  
Wild Type ◽  
Neutrophil Recovery ◽  
Secondary Aml ◽  
Original Trial ◽  
West Midlands ◽  
The Mean

Abstract Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes. Objectives Here we report our experience specifically on patient outcomes and toxicity across 5 Hospitals in West Midlands, UK Methods Patients receiving CPX 351 outcomes were evaluated retrospectively from 2018 to 2021. Baseline genetics, CPX 351 indications, patient's comorbidities, overall survival, remission status, number of cycles delivered, early mortality, reasons for early discontinuation, intensive care admission and time for neutrophil recovery (&gt;0.5) was recorded. Time-to-event outcomes reported here are from a data cut on 01-06-21 Results In a total cohort of 57 patients baseline characteristics are shown on table 1 and compared with the original trial CPX-351 group. Median follow up was 376 days (range 21 to 1248 days). The mean age was 63, 17 patients were under 60, 31 males and 26 females. The most common indication for CPX-351 was AML with antecedent MDS/MPN 51% (N=29), therapy related 14% (N=8), MDS related karyotype (AML-MRC) 19% (N=11) and 16% (N=9) other patients. Mean Charleston co-morbidity score was 2.7 (range 0-6), 10.5% (N=6) had previous non myeloid malignancies, 8.7% (N=5) had prior ischaemic heart disease, only 3.5% (N=2) had ejection fractions under 50%. The most common mutations were TP53 21% (N=12), ASXL1 15.7% (N=9), TET2 15.7% (N=9), IDH2 10.5% (N=6), RUNX1 10.5% (N=6), SRSF2 7% (N=4), JAK2 3.5% (N=2), FLT3 5% (N=3), NPM1 5%(N=3) and IDH1 5% (N=3). MRC cytogenetic risk was adverse in 19 patients (33%), intermediate in 35 patients (61%) and favourable in 3 patients (5%). 30 patients (53%) had adverse European Leukaemia Network classification, 17 (30%) had intermediate and 10 (17%) had favourable. 30-day mortality was 3/57 (5%), 60-day mortality was 6 (10.5%) comparable to the 5.9% and 10.6% rates for the original trial. 9% or 5/57 patients were admitted to ITU with 2 survivors beyond 60 days. Neutropenic fever requiring antibiotics was 100% whereas only 5/57 (9%) had radiological evidence of fungal infection. Only one patient died from COVID 19. The mean time to neutrophil recovery was 35 days with a range of 12 to 84 days. 29 patients completed 1 cycle, 25 completed 2 cycles, only 3 completed 3 cycles. The reasons for stopping were death, refractory disease, drop in performance status, alternative chemotherapy chosen or moving to transplantation (39%). Composite remission rate including CRi was 61% 36/57, adverse ELN group demonstrated 50% 15/30, intermediate 76% 13/17 and favourable 80% 8/10. Mutated P53 was associated with a 50% 6/12 rate whereas in wild type P53 the remission rate was 60% 30/45. Overall median survival from diagnosis was 429 days [95% CI 274 to 788 days]. To compare with the original trial, we removed the under 60s and those with less than 1 year follow up, in this cohort of 30 patients the median survival was 289 days (9.5 months) with 95% CI of 255 to 476 days. P53 mutated patients had an estimated median survival of 257 days versus wild type p53 with 524 days hazard ratio of 2.418 (CI 1.077 to 5.248) with p value of 0.032. Median survival for ELN groups was 373 days (adverse), 413 days (intermediate) and not reached for favourable. Of the 36 patients who achieved a remission, 22 went on to receive an allogenic transplant with follow from 254 to 1248 days, median survival estimated 706 days (95% CI 429-not reached). Patients in remission who haven't received a transplant have a similar estimated survival of 788 days (305-not reached) pending longer follow up. Conclusion This is the first UK multicentre analysis to show comparable results to the landmark trial (median survival 9.5 months in equivalent cases). The improved overall remission rate 61% versus the 47% in the trial and the longer median survival 14 months versus 9.5 months in the trial is expected given the younger age and increase in favourable risk genetics. This study therefore supplies further data of CPX-351 efficacy in younger patients not included in the original studies and may now be used as a standard comparator arm. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

MicroRNA-21 enhances estradiol production by inhibiting WT1 expression in granulosa cells

2021 ◽  
Author(s):  
Renee Emily Hilker ◽  
Bo Pan ◽  
Xiaoshu Zhan ◽  
Julang Li
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Negative Control ◽  
Luciferase Reporter ◽  
Wild Type ◽  
Aromatase Expression ◽  
Antral Follicles ◽  
Porcine Granulosa Cells ◽  
In The Wild ◽  
Type 3

In antral follicles, transition of proliferative granulosa cells to estradiol-producing is critical for proper oocyte maturation. MicroRNAs are noncoding RNAs that play important roles in ovarian follicular development, however this has yet to be fully characterized. MicroRNA-21 is significantly higher in granulosa cells isolated from large antral follicles compared to those from small antral follicles. To investigate the function of miR-21, porcine granulosa cells were transfected with miR-21 mimic or miR-21 targeted siRNA. Cells with the miR-21 mimic had higher aromatase expression and estradiol production but decreased WT1 expression. Conversely, cells with the miR-21 siRNA secreted less estradiol and had higher WT1 expression. We hypothesized miR-21 promotes estradiol production by inhibiting WT1 protein synthesis. We found a potential miR-21 binding site in the 3’UTR of the WT1 transcript and performed a dual luciferase reporter assay using the wild-type and mutated 3’UTR. Compared to the negative control, the miR-21 mimic induced a significant decrease in luciferase activity in the wild-type 3’UTR. This decrease was reversed when the 3’UTR was mutated, suggesting miR-21 targets this site to inhibit WT1 expression. We next transfected porcine granulosa cells with WT1 targeted siRNA and observed a significant increase in aromatase expression and estradiol secretion. We propose that miR-21 represses WT1 expression in granulosa cells to potentially promote aromatase expression and estradiol production. This study offers the first report of a microRNA regulating WT1 expression in granulosa cells and reveals the role of miR-21 in WT1’s regulation of estradiol production.

Follicular development, steroidogenesis and gonadotrophin secretion in response to long-term treatment with a gonadotrophin-releasing hormone agonist in the rat

1995 ◽  
Vol 146 (2) ◽  
pp. 349-357 ◽  
Author(s):  
R K Srivastava ◽  
A Krishna ◽  
R Sridaran
Keyword(s):  
Follicular Development ◽  
Serum Prolactin ◽  
Releasing Hormone ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Progesterone Production ◽  
Significant Attenuation ◽  
Gonadotrophin Releasing Hormone

Abstract Gonadotrophin-releasing hormone (GnRH) and its agonists are implicated in the local control of rat ovarian function. We have evaluated the effects of long-term administration of different doses of GnRH agonist (GnRH-Ag) in vivo (a) on reproductive cyclicity and follicular development, (b) on peripheral gonadotrophin and steroid concentrations and (c) on in vitro cAMP and progesterone production by the follicles in response to stimulatory doses of FSH or LH (1 μg/ml). GnRH-Ag (0·2, 1 or 5 μg/day) administration for 28 days had a profound impact on the oestrous cycle of rats as revealed by vaginal cytology. GnRH-Ag treatment caused a decrease in ovarian and uterine weights, which correlated very well with the decrease in the number of follicles present in the ovary. GnRH-Ag (5 μg/day) reduced the number of early preantral follicles and there was complete disappearance of early as well as late antral follicles. However, a dose of 1 μg GnRH-Ag/day was effective in the complete demise of only late antral follicles with a significant attenuation in the number of early antral follicles. There was an enhancement in serum LH concentrations in response to the highest dose of GnRH-Ag administration with serum FSH concentrations declining in rats treated with the two higher doses. However, serum prolactin concentrations were attenuated only in rats treated with the highest dose of GnRH-Ag. GnRH-Ag treatment decreased serum progesterone and oestradiol concentrations. Preantral follicles obtained from the rats treated with 0·2 or 1 μg GnRH-Ag/day resulted in an attenuated response to LH-or FSH-stimulated progesterone production, whereas antral follicles showed an exaggerated response to the stimulatory doses of FSH in vitro. Antral follicles obtained from the rats treated with 0·2 μg/day showed a robust decrease in cAMP accumulation in response to LH with a slight decrease only with FSH. In contrast, preantral follicles obtained from GnRH-Ag-treated rats did not show any significant attenuation in cAMP production. These data suggest that GnRH-Ag exerts a direct inhibitory effect on follicular development and steroidogenesis and as a result it interferes with the normal oestrous cyclicity in the rat. Journal of Endocrinology (1995) 146, 349–357

Impact of K-ras status on FOLFOX and XELOX regimens efficacy in metastatic colorectal (mCRC) patients (pts).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14674-e14674
Author(s):  
Mikhail Fedyanin ◽  
Alexey Tryakin ◽  
Ilya Pokataev ◽  
Igor Bazin ◽  
Vechaslav Aliev ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Predictive Value ◽  
Prognostic Significance ◽  
Pcr Analysis ◽  
Wild Type ◽  
End Point ◽  
Type K ◽  
Ras Status ◽  
The Mean

e14674 Background: Predictive value of K-ras status for the treatment with anti-EGFR monoclonal antibodies is well established. There is a lack of data about predictive significance of K-ras status for oxaliplatin-based chemotherapy (CT). We retrospectively studied prognostic and predictive significance of mutant K-ras in mCRC pts treated with FOLFOX or XELOX in 1st line CT. Methods: We analyzed data on 127 pts with mCRC, who were treated in our department during 2008-2011 with oxaliplatin-based regimens. K-ras status was determined by PCR analysis in 51/127 (40,1%) pts. Mutant K-ras was detected in 16/51 (31,3%) pts: 13/16 (81,3%) – codon 12, 3/16 (18,7%) – codon 13. mFOLFOX6 was administered in 21/51 (41,2%), XELOX – in 30/51 (58,8%) pts. No pts received anti-EGFR mAb in the 1-st line. Median follow-up was 9 months (range, 2 - 41). The mean number of courses was 9 and 5 in FOLFOX and XELOX groups, respectively. PFS was chosen as a primary end-point. Results: Median PFS was 7,5 months for all 127 pts, 8,4 months in pts with FOLFOX and 7,5 months in pts with XELOX. Median PFS in pts with wild type K-ras was 10,3 months and 6,5 months in pts with mutant K-ras (p=0,1, HR 1,7, 95%CI 0,9-3,4). Negative prognostic significance of mutant K-ras was seen in XELOX group (PFS, 10,9 vs 5,7 months, р= 0,002) but not in FOLFOX group (PFS, 7,7 vs 9,3 months, р= 0,48). In pts with wild type K-ras XELOX lead to longer PFS than FOLFOX regimen - 10,9 vs 7,5 months, respectively (р=0,09, HR 0,52, 95%CI 0,23-1,14). And vice versa, in pts with mutant K-ras FOLFOX was more active than XELOX – median PFS was 9,3 vs 5,7 months, respectively (р=0,009, HR 0,3, 95%CI 0,05-0,64). Conclusions: Our findings probably suggest that K-ras status influences the efficacy of FOLFOX and XELOX regimens in mCRC pts. These data need to be confirmed in larger series of pts.

scholarly journals Expression of Anti-Mullerian Hormone Protein during Early Follicular Development in the Primate Ovary in Vivo Is Influenced by Suppression of Gonadotropin Secretion and Inhibition of Vascular Endothelial Growth Factor

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2273-2281 ◽  
Author(s):  
Fiona H. Thomas ◽  
Evelyn E. Telfer ◽  
Hamish M. Fraser
Keyword(s):  
Gnrh Antagonist ◽  
Follicular Development ◽  
Follicular Phase ◽  
Vascular Endothelial ◽  
Gonadotropin Secretion ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Endothelial Growth Factor ◽  
Vegf Trap

Anti-Mullerian hormone (AMH) plays a role during early follicular development and selection. The aim of this study was to determine the pattern of AMH protein expression in the marmoset ovary and to investigate the effects of inhibition of gonadotropins or vascular endothelial growth factor (VEGF) activity on AMH expression in vivo. GnRH antagonist or VEGF Trap, a soluble decoy receptor, was administered on d 0 or 5 of the follicular phase of the cycle, and ovaries were collected at the end of the follicular phase (d 10). AMH protein was expressed in the marmoset ovary in granulosa cells from the primary stage, with the most abundant staining at the preantral and early antral stages. Inhibition of gonadotropin secretion or VEGF activity between d 0–10 of the cycle decreased AMH expression in early preantral follicles (P &lt; 0.01), and AMH expression was decreased in late preantral follicles in the presence of the VEGF Trap (P &lt; 0.01), compared with controls. There was significantly less AMH expression in early antral follicles with both treatments (P &lt; 0.01), and a decrease in the ratio of oocyte-associated/basement-membrane-associated granulosa cell expression of AMH (P &lt; 0.05). When treatments were administered from d 5–10 of the cycle, both VEGF Trap and GnRH antagonist decreased AMH expression in preantral follicles (P &lt; 0.01) but had no significant effect on early antral follicles. In conclusion, VEGF and gonadotropins are involved in the regulation of expression of AMH in the marmoset. This AMH expression may be a marker of abnormal folliculogenesis in the absence of gonadotropin stimulation or functional angiogenesis.

scholarly journals Clinical, radiological, and histological outcomes after the fibrin–matrix autologous chondrocyte implantation for chondral lesions of the knee in patients more than 50 years old: A prospective case series with minimum 2-year follow-up

2019 ◽  
Vol 28 (1) ◽  
pp. 230949901989350
Author(s):  
Myung Ku Kim ◽  
Jun Sung Park ◽  
Yun Moon Jeon ◽  
Yoon Sang Jeon
Keyword(s):  
Older Patients ◽  
Autologous Chondrocyte Implantation ◽  
Histological Analysis ◽  
Hyaline Cartilage ◽  
Chondral Lesions ◽  
Fibrin Matrix ◽  
Chondrocyte Implantation ◽  
The Mean ◽  
Autologous Chondrocyte

Background: The purpose of this study was to evaluate clinical and radiological outcomes and to analyze the histological findings of repaired cartilage in patients more than 50 years old with underwent fibrin–matrix autologous chondrocyte implantation (ACI). Methods: From January 2013 to February 2014, a prospective study was conducted on 16 patients (16 knees) who underwent fibrin–matrix ACI for International Cartilage Repair Society grade 3 or 4 chondral lesions of the knee. The major lesion was in the medial femoral condyle in all patients. The mean age of the patients was 58.1 ± 6.2 (range 51–66) years, and the minimum follow-up period was 2 years. All patients had clinical and radiological evaluations at 3 months, 6 months, 1 year, and 2 years after surgery. Twelve patients had second-look arthroscopies at 1 year after surgery, and implanted chondral biopsies were performed in 11 of these 12 patients for histological analysis. Results: Functional disability assessment scales for the knee significantly improved after fibrin–matrix ACI ( p < 0.05). The visual analog scale score significantly decreased from 6.7 ± 1.2 to 2.0 ± 1.8 ( p < 0.001). The mean modified magnetic resonance observation of cartilage repair tissue score was 83.8 ± 17.3 at 1 year after surgery and 74.0 ± 19.2 at 2 years after surgery. Repair of the tissue with hyaline cartilage was confirmed histologically. Conclusions: Satisfactory clinical and radiological outcomes were obtained from gel-type fibrin–matrix ACI technique in older patients with a cartilage defect of the knee. Histological analysis confirmed that the new repaired tissue with hyaline cartilage filled the cartilage defect area. Therefore, fibrin–matrix ACI is believed to be an applicable treatment for older patients with chondral lesions of the knee. Level of evidence: Level IV.

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.

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