An update on familial nonmedullary thyroid cancer.
Familial nonmedullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancer cases. FNMTC is divided into two groups: syndromic and nonsyndromic. Nonsyndromic FNMTC is more common as compared with syndromic FNMTC. In syndromic FNMTC, patients are at risk of nonmedullary thyroid cancer (NMTC) and other tumors, and the susceptibility genes are known. In nonsyndromic FNMTC, NMTC is the major feature of the disease and occurs in isolation with an autosomal dominant pattern of inheritance and variable penetrance. New data have emerged on the genetics, clinical characteristics, and outcomes of patients with FNMTC that may have clinical relevance in the management of patients. In this review, we focus on newly characterized syndromic FNMTC entities, criteria for screening and surveillance of nonsyndromic FNMTC, and the classification of nonsyndromic FNMTC as well as the genetic background and heterogeneity of nonsyndromic FNMTC.
View details for DOI 10.1007/s12020-020-02250-3
View details for PubMedID 32162184
Incidence of metastasis and prostate-specific antigen levels at diagnosis in Gleason 3+4 versus 4+3 prostate cancer.
; 10 (2): 203–8
The aim is to assess for a difference in the incidence of metastasis (IM) and prostate-specific antigen (PSA) levels at diagnosis in patients with Gleason score (GS) 3+4 versus 4+3 prostate cancer using a large veterans affairs database.A retrospective review of 1402 medical records from 5 VA hospitals was conducted. The study period was from 2009 to 2014. Primary endpoints were IM and PSA levels at diagnosis. A secondary endpoint was overall survival.Chi-square tests for categorical variables, Student's t-test for continuous, normally distributed variables, and rank sum tests for continuous nonnormally distributed variables.There were 1050 patients with GS3+4 and 352 with GS4+3. There were no differences in sociodemographic and clinical characteristics of the study population. PSA at the time of diagnosis was significantly higher in the GS4+3 patients compared to GS3+4 (18.0 vs. 11.4, respectively; P < 0.001). The IM at diagnosis was higher in the GS4+3 patients (10/352) compared to GS3+4 (9/1041) (2.8% vs. 0.9%; P = 0.005). In an adjusted model, GS4+3 was associated with higher PSA, higher IM at diagnosis. There was no difference in overall survival between the 2 groups though a 23% reduction in overall survival in the GS4+3 was noted (P = 0.53).Our results indicate that patients with GS4+3 prostate cancers have higher PSA levels at diagnosis. GS4+3 is associated with 3-fold increased risk of IM at diagnosis than GS3+4 though the overall incidence is low. Further research is needed to assess whether GS4+3 patients need routine staging imaging investigations at the time of diagnosis similar to patients with higher Gleason scores (GS ≥8).
View details for PubMedID 29719335
View details for PubMedCentralID PMC5907332
- Physician Wellness in Surgical Residency CURRENT SURGERY REPORTS 2018; 6 (1)
Rectal gastrointestinal stromal tumor with metastasis to the penis: Case report and review of literature.
International journal of surgery case reports
2016; 29: 172-175
We report the case of a 51-year-old gentleman with previously diagnosed gastrointestinal stromal tumor (GIST) of the rectum with metastasis to the penis. The patient underwent abdominoperineal resection of the primary tumor with negative margins and completed a three-year course of imatinib mesylate (Gleevec). Forty months after resection of his rectal tumor, the patient presented to his urologist with worsening testicular pain, mild lower urinary tract obstructive symptoms, and nocturia. A pelvic MRI revealed the presence of an ill-defined mass in the right perineum extending from the base of the penis to the penoscrotal junction. Biopsy of this mass was consistent with metastatic GIST. To our knowledge, this is the first report of metastatic GIST to the penis.
View details for DOI 10.1016/j.ijscr.2016.11.006
View details for PubMedID 27865145
View details for PubMedCentralID PMC5120263
Knowledge, Attitude, and Practices Regarding Vector-borne Diseases in Western Jamaica
ANNALS OF GLOBAL HEALTH
2015; 81 (5): 654-663
Outbreaks of vector-borne diseases (VBDs) such as dengue and malaria can overwhelm health systems in resource-poor countries. Environmental management strategies that reduce or eliminate vector breeding sites combined with improved personal prevention strategies can help to significantly reduce transmission of these infections.The aim of this study was to assess the knowledge, attitudes, and practices (KAPs) of residents in western Jamaica regarding control of mosquito vectors and protection from mosquito bites.A cross-sectional study was conducted between May and August 2010 among patients or family members of patients waiting to be seen at hospitals in western Jamaica. Participants completed an interviewer-administered questionnaire on sociodemographic factors and KAPs regarding VBDs. KAP scores were calculated and categorized as high or low based on the number of correct or positive responses. Logistic regression analyses were conducted to identify predictors of KAP and linear regression analysis conducted to determine if knowledge and attitude scores predicted practice scores.In all, 361 (85 men and 276 women) people participated in the study. Most participants (87%) scored low on knowledge and practice items (78%). Conversely, 78% scored high on attitude items. By multivariate logistic regression, housewives were 82% less likely than laborers to have high attitude scores; homeowners were 65% less likely than renters to have high attitude scores. Participants from households with 1 to 2 children were 3.4 times more likely to have high attitude scores compared with those from households with no children. Participants from households with at least 5 people were 65% less likely than those from households with fewer than 5 people to have high practice scores. By multivariable linear regression knowledge and attitude scores were significant predictors of practice score.The study revealed poor knowledge of VBDs and poor prevention practices among participants. It identified specific groups that can be targeted with vector control and personal protection interventions to decrease transmission of the infections.
View details for DOI 10.1016/j.aogh.2015.08.013
View details for Web of Science ID 000373193900010
View details for PubMedID 27036722
View details for PubMedCentralID PMC4818946
- NEEDLE-FREE SUBCUTANEOUS SELF INJECTION FOR TESTOSTERONE SUPPLEMENTATION THERAPY ELSEVIER SCIENCE INC. 2015: E772
Axon degeneration is key component of neuronal death in amyloid-beta toxicity
2013; 63 (8): 782-789
Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid β (Aβ) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aβ1-42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the Aβ-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in Aβ1-42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in Aβ1-42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of Aβ1-42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer's disease.
View details for DOI 10.1016/j.neuint.2013.08.013
View details for Web of Science ID 000328872300008
View details for PubMedID 24083988
View details for PubMedCentralID PMC3918889
Endonuclease G mediates endothelial cell death induced by carbamylated LDL
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2011; 300 (6): H1997-H2004
End-stage kidney disease is a terminal stage of chronic kidney disease, which is associated with a high incidence of cardiovascular disease. Cardiovascular disease frequently results from endothelial injury caused by carbamylated LDL (cLDL), the product of LDL modification by urea-derived cyanate. Our previous data suggested that cLDL induces mitogen-activated protein kinase-dependent mitotic DNA fragmentation and cell death. However, the mechanism of this pathway is unknown. The current study demonstrated that cLDL-induced endothelial mitotic cell death is independent of caspase-3. The expression of endonuclease G (EndoG), the nuclease implicated in caspase-independent DNA fragmentation, was significantly increased in response to cLDL exposure to the cells. The inhibition of EndoG by RNAi protected cLDL-induced DNA fragmentation, whereas the overexpression of EndoG induced more DNA fragmentation in endothelial cells. Ex vivo experiments with primary endothelial cells isolated from wild-type (WT) and EndoG knockout (KO) mice demonstrated that EndoG KO cells are partially protected against cLDL toxicity compared with WT cells. To determine cLDL toxicity in vivo, we administered cLDL or native LDL (nLDL) intravenously to the WT and EndoG KO mice and then measured floating endothelial cells in blood using flow cytometry. The results showed an increased number of floating endothelial cells after cLDL versus nLDL injection in WT mice but not in EndoG KO mice. Finally, the inhibitors of MEK-ERK1/2 and JNK-c-jun pathways decreased cLDL-induced EndoG overexpression and DNA fragmentation. In summary, our data suggest that cLDL-induced endothelial toxicity is caspase independent and results from EndoG-dependent DNA fragmentation.
View details for DOI 10.1152/ajpheart.01311.2010
View details for Web of Science ID 000291209300004
View details for PubMedID 21460199
View details for PubMedCentralID PMC3119093