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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 217 records · Page 12Linked to original sources
PubMed1998

Toxic digoxin-drug interactions: the major role of renal P-glycoprotein.

The clinical use of digoxin is complicated by a large number of drug interactions leading to severe toxicity of the cardiac glycoside. The discovery that digoxin is actively secreted by the renal tubular cell via the p-glycoprotein drug efflux pump has led us to examine whether commonly interacting drugs do so by inhibiting renal tubular secretion of digoxin. We review digoxin-drug interactions which have been studied kinetically in humans, where there are sufficient data on renal clearance of digoxin and GFR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Fetal alcohol syndrome. Role of the family physician.

QuestionOne of my female patients drinks heavily. Although she is not planning to conceive, I worry that her lifestyle might lead to pregnancy and danger for her fetus. What do you recommend?AnswerYou should counsel your patient on effective contraception and advise her about the advantages of the various methods available.

Adolescent↗
PubMed1998

Breast cancer during pregnancy. Approach to rational management.

QUESTION: A 35-year-old woman attending my clinic in the 20th week of pregnancy had a lump in her breast. Open biopsy revealed ductal carcinoma. Radical mastectomy with axillary lymph node biopsy showed three out of 10 nodes positive. What are the short- and long-term implications of chemotherapy during pregnancy? ANSWER: Patients with breast cancer during pregnancy should be treated using the same criteria as their nonpregnant counterparts, with the modifications required by pregnancy. The benefits of the diagnostic workup and use of chemotherapy, radiotherapy, and surgery have to be weighed carefully against their risk to the unborn baby.

Abnormalities, Drug-Induced↗
PubMed1998

Is topical tretinoin safe during the first trimester?

QUESTIONOne of my patients conceived while using a topical tretinoin preparation for acne. I know this drug is related to Accutane, which is teratogenic. How should I advise her?ANSWERAvailable evidence suggests that topical tretinoin does not increase teratogenic risk in humans.

Abnormalities, Drug-Induced↗
PubMed1998

Managing exposure to chickenpox during pregnancy. New program.

QUESTION: Every year several of my pregnant patients ask me what to do about being exposed to a child who later comes down with chickenpox. What is your recommendation? ANSWER: Whether or not a mother had chickenpox in childhood often does not accurately determine her immunity. A rapid test, such as the latex agglutination test, is useful. If test results are negative, or if testing is not feasible, varicella zoster immunoglobulin should be administered within 96 hours of exposure.

Chickenpox↗
PubMed1998

Counseling psychiatric patients about drug exposures during pregnancy.

QUESTIONSeveral of my patients with psychiatric disorders are either planning to conceive or are already pregnant. I find it difficult to reassure them about the safety of taking medications during pregnancy. How do you deal with such situations at Motherisk?ANSWERThese patients should be counseled in an unambiguous and consistent manner. They can be referred to the Motherisk Program, or Motherisk can fax up-to-date information to their physicians.

Adult↗
PubMed1998

Therapeutic approach to hypertension during pregnancy.

QuestionQuite a few of my pregnant patients have hypertensive disorders. What is the threshold for treating hypertension during pregnancy? Which of the various antihypertensive agents are considered safe during pregnancy?AnswerPharmacologic therapy could benefit mother and baby when diastolic pressure exceeds 110 mm Hg. Preeclampsia must be followed closely. Methyldopa (eg, Aldomet) and hydralazine (eg, Apresoline) are still the drugs of choice during pregnancy, although the safety and efficacy of calcium channel blockers and Beta-blockers appear well established.

Antihypertensive Agents↗
PubMed1998

Pharmacologic treatment of nausea and vomiting during pregnancy.

QUESTIONSome of my pregnant patients have trouble functioning because of morning sickness. In particular, they are afraid to take medications. They end up losing weight, quitting work, and dropping out of other activities. What can I do to allay their fears?ANSWERWomen often benefit from knowing that they are not alone in having this problem, that morning sickness typically does not harm a fetus, and that safe therapies are available. Psychological and medical support is very important. Other causes of nausea and vomiting must always be ruled out. The Motherisk Program has a clinic and hot-line line for patients with severe morning sickness.

Abnormalities, Drug-Induced↗
PubMed1998

Rationale for treating pregnant smokers with nicotine patches.

QUESTION: One of my pregnant patients smokes about 20 cigarettes daily. She has tried several times through behavioural therapy to quit, but has been unsuccessful. What do you recommend? ANSWER: You might consider nicotine replacement therapy and concurrent behavioural counseling. With this therapy, nicotine levels in the body are typically lower than during heavy smoking, and the thousands of other toxins emitted by cigarette smoke, such as carbon monoxide and hydrogen cyanide, are avoided.

Administration, Cutaneous↗
PubMed1998

Valproic acid use in psychiatry: issues in treating women of reproductive age.

Valproic acid, a well known anticonvulsant, is being used by psychiatrists increasingly to manage bipolar and other affective disorders. Because of the demographics of the population affected by such psychiatric conditions, more women of childbearing age are likely to be exposed to this teratogenic drug. Neural tube defects (NTD) are the most common of the major anomalies associated with in utero valproic acid exposure, and are estimated to occur in 1% to 2% of exposed fetuses. Other teratogenic effects include facial dysmorphism, congenital cardiac defects, limb reduction defects and other skeletal anomalies. Prenatal diagnosis, in particular maternal serum alpha-fetoprotein screening and targeted ultrasonography, should be offered to all pregnant women exposed to valproic acid and couples need to be aware of the prenatal diagnostic options available to them. Periconceptual prophylaxis with high doses of folic acid is recommended for all women on valproic acid and counselling should also emphasize planning pregnancy to optimize folic acid supplementation. Psychiatrists should be aware of the teratogenic potential of valproic acid and know how to counsel their patients of reproductive age.

Adult↗
PubMed1998

Are the new SSRIs safe for pregnant women?

QUESTION: More and more of my female patients are switching to the new selective serotonin reuptake inhibitors. Are they safe during pregnancy? ANSWER: Our data suggest these drugs do not increase the malformation rate, but there are no data on neurodevelopment. Because such data do exist on fluoxetine and tricyclic antidepressants, those drugs should be considered first.

Abnormalities, Drug-Induced↗
PubMed1998

How long should someone wait after CMV infection to start pregnancy?

QUESTION: One of my patients contracted a primary cytomegalovirus (CMV) infection. What is the recommended waiting time between primary CMV infection and conception, and which tests are valid for determining whether infectivity is over? ANSWER: Although no data on the proper waiting period between primary CMV infection and conception are available, we suggest waiting until CMV-specific immunoglobulin G antibodies are present (at least 6 months).

Cytomegalovirus Infections↗
PubMed1998

Do silicone breast implants affect breastfeeding?

QUESTION: One of my patients has silicone breast implants. She gave birth to a healthy baby boy but is afraid to breastfeed because she read in a magazine that the baby might be affected by silicone secreted in the milk. How should I advise her? ANSWER: Neither silicone nor its components could be measured in the breast milk of women with silicone implants. Your patient should be able to breastfeed safely.

Adult↗
PubMed1997

Degradation of the inducible cAMP early repressor (ICER) by the ubiquitin-proteasome pathway.

The inducible cAMP early repressor (ICER) is a powerful transcriptional inhibitor that plays an important role in the regulation of the cAMP-dependent transcriptional response in the neuroendocrine system. ICER activity is primarily determined by its intracellular concentration, rather than by post-translational modifications, such as phosphorylation. We investigated the mechanisms that regulate the levels of ICER transcript and polypeptides in cardiocytes, myogenic (C2C12) and pituitary-derived (GH3) cell lines. We show that in primary cardiocytes and GH3 cells ICER was inducible by cAMP but not by membrane depolarization. Moreover, lactacystin, a specific proteasome inhibitor, decreased the rate of ICER degradation. This effect was associated with the accumulation of ICER-ubiquitin conjugates. We conclude that the intracellular levels of ICER are controlled by the ubiquitin-proteasome pathway for protein breakdown.

Acetylcysteine↗
PubMed1997

A cellular model for long QT syndrome. Trapping of heteromultimeric complexes consisting of truncated Kv1.1 potassium channel polypeptides and native Kv1.4 and Kv1.5 channels in the endoplasmic reticulum.

We demonstrated that overexpression of a cRNA encoding a truncated potassium channel polypeptide that contains the NH2 terminus and the first transmembrane segment (Kv1.1N206Tag) abolished the expression of Kv1.1 and Kv1.5 outward currents in Xenopus oocytes (Babila, T., Moscucci, A., Wang, H., Weaver, F. E. & Koren, G. (1994) Neuron 12, 615-626). Recently, we showed that expression of Kv1.1N206Tag in the heart of transgenic mice resulted in the creation of mice with prolongation of the surface electrocardiogram's QT interval (London, B., Han, X., Folco, E. & Koren, G. (1996) Biophys. J. 70, A2601). To study the dominant negative mechanism of Kv1.1N206Tag, we overexpressed it in GH3 cells, a pituitary cell line expressing Kv1. 5 and Kv1.4. RNase protection analysis comparing the steady-state levels of native Kv1.5 and Kv1.1N206Tag transcripts revealed an excess of Kv1.1N206Tag transcript. Immunoprecipitation analysis using 12CA5 monoclonal antibody detected a 25-kDa polypeptide in the transfected cells. The half-life of Kv1.1N206Tag was 2.6 h. Subcellular fractionation of cell lysates labeled with [35S]methionine revealed that Kv1.1N206Tag polypeptide is detectable in the particulate (membranous) fraction, but not in the soluble (cytosol) fraction. A series of double immunoprecipitations with 12CA5 and polyclonal antibodies against Kv1.5 and Kv1.4 revealed that Kv1.1N206Tag forms heteromultimeric complexes with the native Kv1.4 and Kv1.5 polypeptides. The steady-state levels of Kv1.5 were not affected by the overexpression of Kv1.1N206Tag. Immunofluorescence colocalization and confocal microscopy analyses revealed that Kv1.1N206TagFlag did not reach the plasma membrane, and its distribution pattern was characteristic to that of a resident endoplasmic reticulum polypeptide. Our observations establish that the negative effect of Kv1.1N206Tag is mediated by the formation of heteromultimeric complexes with the native channels and by the retention of these complexes in the endoplasmic reticulum.

Animals↗