ABSTRACT
Rudimentary horn ectopic pregnancies are uncommonly encountered in women with müllerian duct anomalies. The clinical presentation of this entity is nonspecific, giving ultrasound a critical role in making the diagnosis. Timely diagnosis and management of rudimentary horn ectopic pregnancies are pivotal in reducing the high rates of uterine rupture and maternal mortality historically associated with this condition.
Subject(s)
Mullerian Ducts/abnormalities , Pregnancy, Cornual/diagnostic imaging , Ultrasonography, Prenatal/methods , Adolescent , Adult , Female , Humans , Mullerian Ducts/diagnostic imaging , Pregnancy , Retrospective Studies , Uterus/diagnostic imagingABSTRACT
AIMS/HYPOTHESIS: Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications. METHODS: We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11 mutations identified through the University of Chicago Monogenic Diabetes Registry ( http://monogenicdiabetes.uchicago.edu/registry ). We assessed the influence of age at initiation of SU therapy on treatment outcomes. RESULTS: HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg(-1) day(-1)) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported. CONCLUSIONS/INTERPRETATION: Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes.
Subject(s)
Diabetes Mellitus/congenital , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Potassium Channels, Inwardly Rectifying/genetics , Sulfonylurea Compounds/therapeutic use , Adolescent , Adult , Age Factors , Age of Onset , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Glyburide/therapeutic use , Glycated Hemoglobin/analysis , Humans , Infant , Infant, Newborn , Male , Mutation/genetics , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.
