Clinicopathologic Features of NSCLC Diagnosed During Pregnancy or the Peripartum Period in the Era of Molecular Genotyping.

INTRODUCTION: Cancer will be diagnosed in one in 1000 women during pregnancy. The outcomes of NSCLC diagnosed during pregnancy are dismal, with most patients dying within 1 year. Actionable mutations are more likely to be found among younger patients with NSCLC. However, most previous reports of NSCLC diagnosed during pregnancy did not include molecular genotyping. METHODS: We performed a retrospective analysis of patients seen at our institution between 2009 and 2015 to identify women in whom NSCLC was diagnosed during pregnancy or the peripartum period and determined clinicopathologic features, including molecular genotype. RESULTS: We identified 2422 women with NSCLC, including 160 women of reproductive age. Among the women of reproductive age, eight cases of NSCLC diagnosed during pregnancy or the peripartum period were identified; all were diagnosed in minimal or never-smokers with metastatic adenocarcinoma. Six of these patients were found to have anaplastic lymphoma kinase gene (ALK) rearrangements, whereas the remaining two were EGFR mutation positive. We observed a borderline significant association between a diagnosis of NSCLC during pregnancy or the peripartum period and ALK positivity (p = 0.053). All eight women in whom NSCLC was diagnosed during pregnancy or the peripartum period received treatment with genotype-directed therapies after delivery. The median overall survival has not been reached at a median follow-up of 30 months. CONCLUSIONS: Although a diagnosis of NSCLC during pregnancy or the peripartum period is rare, diagnostic evaluation should not be delayed in pregnant women presenting with symptoms worrisome for lung cancer. Evaluation should include testing for targetable molecular alterations.

Alterations of fatty acid ß-oxidation capability in the liver of ketotic cows.

Dairy cows are highly susceptible to ketosis after parturition. In the present study, we evaluated the expression of fatty acid ß-oxidation-related enzymes in the liver of ketotic (n=6) and nonketotic (n=6) cows. Serum levels of nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and glucose were determined by using standard biochemical techniques. The mRNA abundance and protein content of acyl-CoA synthetase long-chain (ACSL), carnitine palmitoyltransferase I (CPT I), carnitine palmitoyltransferase II (CPT II), acyl-CoA dehydrogenase long chain (ACADL), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS), and acetyl-CoA carboxylase (ACC) were evaluated by real-time PCR and ELISA. We found that serum glucose levels were lower in ketotic cows than in nonketotic cows, but serum BHBA and NEFA concentrations were higher. Messenger RNA and protein levels of ACSL were significantly higher in livers of ketotic cows than those in nonketotic cows. In contrast, mRNA levels of CPT I and mRNA and protein levels of CPT II, ACADL, HMGCS, and ACC were decreased in the liver of ketotic cows. Serum NEFA concentration positively correlated with ACSL protein levels and negatively correlated with protein levels of CPT II, HMGCS, ACADL, and ACC. In addition, serum BHBA concentration negatively correlated with protein levels of CPT II, HMGCS, and ACADL. Overall, fatty acid ß-oxidation capability was altered in the liver of ketotic compared with nonketotic cows. Furthermore, high serum NEFA and BHBA concentrations play key roles in affecting pathways of fatty acid metabolism in the liver.

Carnitine palmitoyltransferase I in liver of periparturient dairy cows: effects of prepartum intake, postpartum induction of ketosis, and periparturient disorders.

Thirty-five multiparous Holstein cows were used to determine the role of mitochondrial carnitine palmitoyltransferase I (CPT I) in liver on peripartal adaptations of fatty acid metabolism. From dry-off to parturition, cows were fed a diet at either ad libitum (n = 17) or restricted intake (RI, 80% of calculated requirements for net energy; n = 18). After parturition, all cows were fed a lactation diet. At 4 d in milk (DIM), cows underwent a physical examination and were classified as healthy (n = 15) or having at least one periparturient disorder (PD; n = 17). Cows in the healthy group were assigned to either a control (n = 6) group or a ketosis induction (KI; n = 9) group. Cows with periparturient disorders were assigned to a third (PDC; n = 17) group. Cows in control and PDC groups were fed for ad libitum intake. Cows in KI were fed at 50% of their respective intake at d 4 postpartum starting from 5 DIM and continuing to signs of clinical ketosis or until 14 DIM; cows then were returned to ad libitum intake. Liver was biopsied at -30 d, 1 d, at signs of clinical ketosis or 14 d, and 28 d relative to parturition. Mitochondria were isolated by differential centrifugation. Activity of CPT I was 5.4 and 7.6 nmol of palmitoylcarnitine formed per min/mg of protein for ad libitum and RI, respectively, at -30 DIM. Sensitivity of CPT I to its inhibitor, malonyl CoA, did not differ between ad libitum and RI cows. Differences in CPT I activity between ad libitum and RI were no longer significant at 1 DIM. Postpartum CPT I activity and malonyl CoA sensitivity at 1 DIM, onset of clinical ketosis or 14 DIM, and 28 DIM were not affected by prepartum intake (ad libitum vs. RI), postpartum health status (healthy vs. PD), or ketosis induction status (control vs. KI vs. PDC). Activity of CPT I was positively correlated with liver total lipid, liver triglyceride, liver triglyceride to glycogen ratio, and serum nonesterified fatty acids. Activity of CPT I and dry matter intake were not correlated. Prepartum intake affected prepartum CPT I activity but not malonyl CoA sensitivity. Neither induction of primary ketosis nor periparturient disorders greatly affected CPT I activity or sensitivity, which indicates that alterations of CPT I may not be a major factor in the etiology of primary ketosis or other periparturient disorders.

Postpartum "psychosis" in mild argininosuccinate synthetase deficiency.

BACKGROUND: Urea cycle disorders are relatively rare but well-established causes of postpartum coma and death. Such clinical presentations have been reported previously in ornithine transcarbamylase and carbamyl phosphate synthetase deficiencies. CASE: We describe a woman, without prior symptoms of metabolic disease, who presented with hyperammonemia and psychiatric symptoms in the postpartum period. Initial diagnoses included acute fatty liver of pregnancy and postpartum psychosis. She was later found to have argininosuccinate synthetase deficiency after further metabolic investigations. Rare heterozygous mutations in the argininosuccinate synthetase gene were identified. CONCLUSION: Urea cycle disorders may present initially with postpartum psychiatric symptoms and may represent an underrecognized cause of "postpartum psychosis." We recommend obtaining metabolic studies in women with neurologic or severe psychiatric symptoms in the postpartum period.

[Pregnancy, labor and puerperium in patients with HELLP syndrome]. / Przebieg ciazy, porodu i pologu u pacjentek z zespolem HELLP.

OBJECTIVE: The aim of this study was to evaluate retrospectively 10 women with the syndrome of hemolysis, elevated liver enzymes, low platelets (HELLP)--age of patients, quality of antepartum medical care, clinical, biochemical parameters, treatment, course and duration of pregnancies, way of delivery, and puerperium. MATERIAL AND METHODS: Women in the study group were divided in order of platelets (PLT) levels: 4 patients with PLT levels lower than 50 G/l and 6 patients with PLT levels higher than 50 G/l. The mean duration of pregnancies in both groups was similar. RESULTS: In the first group just one women delivered by vaginal route when compared with the cesarean delivery. We noticed lower frequency of antepartum medical visits among the first group. Such signs as vomiting, nausea, abdominal pain, pruritus occurred more frequently in the second group. The most common complication observed in both groups of patients was severe preeclampsia. HELLP syndrome was also observed in the multiple pregnancies. In the study group high blood concentrations of urea, creatinine, total bilirubin, alanine transaminase and aspartate aminotransferase were present. Termination of pregnancy is still recognised to be the best way of HELLP treatment, however the efficacy of steroid drugs administration as conservative treatment were also demonstrated. CONCLUSION: The disseminated intravascular coagulation as the HELLP complication in the puerperium period seems to be a serious problem, which can conduct to the need of hysterectomy.

Relation between post-partum liver dysfunction and anti-cytochrome 2D6 antibodies.

PROBLEM: Autoimmune thyroid disease frequently aggravates or develops after delivery through the immune rebound mechanism. However, little is known about the post-partum development of autoimmune hepatitis (AIH). METHOD OF STUDY: We examined 18 patients who developed liver dysfunction after delivery or abortion. Serial examinations were performed in 10 of these cases. Anti-cytochrome 2D6(CYP2D6) antibodies, which are liver-specific autoantibodies, were measured using a sensitive radioligand assay. RESULTS: Liver dysfunction developed between 1 and 5 months after delivery and was mild and transient except in one case. One patient developed liver dysfunction after abortion. Eight of 10 patients who underwent serial serologic examinations were positive for anti-nuclear antibodies, but anti-smooth muscle antibodies were positive in only three patients, and were present only at low titer. None of the patients had anti-mitochondrial antibodies. Nine of these 10 cases were diagnosed as definite or probable AIH according to the international scoring system of AIH. Nine of these 10 patients were positive for anti-CYP2D6 antibodies. The increase of anti-CYP2D6 antibodies was slightly delayed compared to increase of aminotransferase. Of the 18 patients who developed liver dysfunction, 15 cases (83.3%) were positive for anti-CYP2D6 antibodies. Of the 77 post-partum control subjects only three (3.9%) had positive antibodies. CONCLUSIONS: Autoimmune hepatitis developed after delivery, similarly to the development of post-partum autoimmune thyroid disease. Measurement of anti-CYP2D6 antibodies by a sensitive radioligand assay could provide information important for the detection of post-partum AIH.

Abnormal platelet 5-hydroxytryptamine uptake and imipramine binding in postnatal dysphoria.

Platelet 14C-5-hydroxytryptamine (14C-5-HT) uptake, 3H-imipramine binding and monoamine oxidase (MAO) activity were measured in women 5 days postpartum and compared with depression scores (Edinburgh Postnatal Depression Scale) at that time and 6 weeks later. Mean Km of 14C-5-HT uptake was significantly reduced in the group showing dysphoria at 5 days (p less than 0.01). Mean Kd of 3H-imipramine binding was significantly increased in the group who later went on to become depressed at 6 weeks postpartum (p less than 0.03). Vmax for 14C-5-HT uptake, Bmax for 3H-imipramine binding and MAO activity did not differ between depressed and non-depressed patients on either occasion. Although the observed changes manifested in a system known to be disturbed in other forms of depression, they were in affinity rather than Bmax or Vmax. Even though probably not of direct physiological significance, such results, if confirmed, together with other pointers in the literature, suggest biochemical abnormalities specific to the puerperal period.

Manifestation of familial porphyria cutanea tarda after childbirth.

We report the case of a woman with hereditary porphyria cutanea tarda which manifested 3 weeks after she gave birth to her second child. The mother of the patient had also been diagnosed and treated for porphyria cutanea tarda. Reduced red cell uroporphyrinogen decarboxylase activity was found in the patient, the new-born child and the patient's mother. Normal enzyme activity was found in the patient's first child.

Peripartal changes in serum alkaline phosphatase activity and lactate dehydrogenase activity in dairy cows.

Peripartal serum alkaline phosphatase activity and lactate dehydrogenase activity were measured in 30 dairy cows in order to examine the association between retained fetal membranes and enzyme activity. Daily blood samples were obtained from pregnant cows, starting 15 days before the expected day of calving until eight days after parturition. Sera from 15 cows which retained fetal membranes longer than 24 hours and 15 cows which shed fetal membranes within six hours after parturition were analyzed for alkaline phosphatase and lactate dehydrogenase enzyme activities. Mean alkaline phosphatase enzyme activities ranged from 15.93 to 32.6 U/L in retained and nonretained placenta cows. There was a trend towards higher serum alkaline phosphatase activities in retained placenta cows but the differences were not significant among the groups (P greater than 0.05). Mean lactate dehydrogenase activities ranged from 307.2 to 438.86 U/L in nonretained and retained placenta cows. Lactate dehydrogenase enzyme activities in nonretained and retained placenta cows were similar (P greater than 0.05). The alkaline phosphatase and lactate dehydrogenase enzyme activities peaked at the time of parturition in both groups. However, the differences in alkaline phosphatase and lactate dehydrogenase activities on different days within non-retained and retained placenta cows were significant (P less than 0.05). Results indicate that prepartal changes in alkaline phosphatase and lactate dehydrogenase enzyme activities are not predictive of placental retention postpartum.

Severe preeclampsia with persistent postpartum hemolysis and thrombocytopenia treated by plasmapheresis.

A case of severe preeclampsia in which hemolysis and rapid platelet consumption persisted after delivery, but in which the blood urea nitrogen and serum glutamic oxaloacetic acid transaminase levels returned to normal is presented. Antiplatelet aggregating medications and exchange plasmapheresis with fresh frozen plasma were begun on the eighth postpartum day, but the hemolysis and rapid platelet consumption did not begin to improve until the 12th postpartum day. The use of plasmapheresis in highly selected cases of severe preeclampsia with hemolysis and thrombocytopenia that do not resolve after delivery is discussed.

Sex differences in biological factors putatively related to depression.

Gender differences in the prevalence of affective disorders were suggested by several authorities in the field. Such differences may be attributed to sex-related differences in levels or activity of monoamine transmitters, especially since some of these variables have been shown to be altered by gonadal hormones. The reported association of perimenstrual and postpartum dysphoria, with affective disorders may contribute to further elucidation of pathophysiology of depression in women--in light of the hormonal-behavioral dynamics of these periods. Several factors associated with monoamines biosynthesis, availability, uptake and metabolism were found to be more abnormal in normal and depressed women compared to men. Age-sex differences in some biological markers for depression are reported as well. Their relevance to the underlying pathophysiology of depression is unclear but they may provide clues for further research.

[Development of aspartate aminotransferase, alanine and gamma-glutamyltransferase in the blood serum of dairy cows during the last month of pregnancy and the puerperium in relation to liver function]. / Vývoj aktivit aminotransferáz asparátu AST), alaninu (ALT) a gamaglutamyltransferázy (GMT) v krevním séru dojnic v posledním mesíci brezosti a v puerperiu ve vztahu k jaterním funkcím.

Over the period of two years, the blood serum of dairy cows from three localities was examined repeatedly for the activities of aspartate aminotransferase (EC 2.6.1.1) (AST), alanine aminotransferase (EC 2.6.1.2) (ALT) and gammaglutamyltransferase (EC 2.3.2.1) (GMT). First examinations were performed two to four weeks before the expected term of delivery, the repeated examinations between the sixth and eighth week after delivery. The results obtained were used to calculate AST/ALT and GMT/ALT indexes in the studied group of animals (n = 12). As found out, the decrease in these indexes or the equality of values from the sixth to the eighth week after delivery, as compared with the period of two to four weeks prior to delivery, were connected with the clinically detectable disturbances of puerperium, i. e. inflammable discharge from the reproductive organs of dairy cows; this was observed even in the cases when the enzymatic activity was within the references standards.