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Biomedical subjects

L S Cohen

Publications and source records attributed to L S Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Birth outcomes following prenatal exposure to fluoxetine.

BACKGROUND: Although pregnancy has frequently been described as a time of emotional well-being, some women experience significant antenatal depression that may require treatment with antidepressants. The purpose of this investigation was to examine the relative effects of early and late trimester exposure to fluoxetine and perinatal outcome. METHODS: Obstetric and neonatal records were reviewed for 64 mother-infant pairs where there was documented use of fluoxetine at some point during pregnancy. Differences in several measures of obstetrical outcome and neonatal well-being were examined in early trimester- and late trimester-exposed infants. RESULTS: No differences in birth weight and acute neonatal outcome were evident across the two groups, though there was a higher frequency of special care nursery admissions for infants with exposure to fluoxetine late in pregnancy. Special care nursery admissions could not be attributed to any specific factor. CONCLUSIONS: Given the growing numbers of women who are treated with antidepressants, including fluoxetine, during pregnancy, and the strong association between depression during pregnancy and risk for postpartum depression, patients may be best advised to continue treatment with antidepressants through labor and delivery versus making any change in intensity of treatment during the acute peripartum period.

Adult↗
PubMed2000

The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies.

The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nm range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen.

Amino Acid Sequence↗
PubMed2000

Role of vaginal sonography and hysterosonography in the endoscopic treatment of uterine myomas.

OBJECTIVE: To summarize the advantages and disadvantages of the various imaging techniques used to evaluate uterine leiomyomas preoperatively and to propose a classification system for intramural and subserosal leiomyomas that may better serve the endoscopist in surgical treatment. DESIGN: A MEDLINE search of the available literature was performed. CONCLUSION(S): Selective use of the various imaging techniques is required based on the clinical situation. Classification systems that describe the degree of myometrial involvement are needed for appropriate case selection and counseling by the endoscopist.

Endoscopy↗
PubMed2000

Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance.

OBJECTIVE: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. METHOD: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. RESULTS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%). Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. CONCLUSIONS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium.

Age of Onset↗
PubMed2000

Paroxetine in human breast milk and nursing infants.

OBJECTIVE: The purpose of this study was to determine the extent of infant medication exposure through breast-feeding during maternal treatment with paroxetine. METHOD: Breast milk and paired maternal and infant sera were collected after 10 days of maternal treatment with paroxetine at a stable daily dose (10-50 mg/day). All samples were analyzed by means of high-performance liquid chromatography with ultraviolet detection and a limit of detection of 2 ng/ml. RESULTS: Breast milk paroxetine concentrations were highly variable (2-101 ng/ml) and were present in all breast milk samples (N=108). A significant gradient effect was observed, with greater paroxetine concentrations found in later portions of breast milk (hind milk) than in early portions (fore milk). No clear time course of paroxetine excretion into breast milk was demonstrated, although maternal paroxetine daily dose reliably predicted both trough and peak breast milk concentrations over a 24-hour period. In 16 mother and infant serum pairs, no detectable concentrations of paroxetine were found in the serum of the nursing infants. CONCLUSIONS: This study extends previous data by demonstrating the presence of paroxetine in the breast milk of nursing women treated with this medication. The low concentrations of paroxetine in infant serum and lack of any observable adverse effects after maternal use of this medication while breast-feeding parallels the available data on other selective serotonin reuptake inhibitors.

Breast Feeding↗
PubMed1999

Prevalence and predictors of depressive symptoms in older premenopausal women: the Harvard Study of Moods and Cycles.

BACKGROUND: The Harvard Study of Moods and Cycles is a community-based cohort study designed to evaluate the relationship between major depression and changes in menstrual and ovarian function. METHODS: All women aged 36 to 44 years with a verifiable address from 7 Boston, Mass, metropolitan communities were selected from the Massachusetts Town Books. A self-administered questionnaire assessed demographic characteristics and menstrual history, depression history, and current depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) in 4161 women. RESULTS: We observed a score of 16 or more on the CES-D in 22.4% of women surveyed, and 8.6% scored 25 or more. Widowed, divorced, or separated women were twice as likely as married women to have depression scores greater than 16 (95% confidence interval, 1.6-2.8), and smokers in the upper tertile of pack-years were 1.9 times more likely to have CES-D scores of 16 or more (95% confidence interval, 1.5-2.3). Relative to nulliparous women, those with 1 or 2 children had a 30% lower risk of historic mood disorder, and those with 3 or more children had an even greater reduction in risk (odds ratio, 0.4; 95% confidence interval, 0.3-0.6). Menstrual cycle irregularities were largely unassociated with current or past depression. However, 5 of 8 premenstrual symptoms were significantly associated with CES-D scores of 16 or more. CONCLUSIONS: These findings corroborate the prevalence of depression reported by other community-based studies, and also support a relationship between depressive symptoms and marital status, cigarette smoking, nulliparity, and premenstrual symptoms.

Adult↗
PubMed1999

Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome.

Many women experience symptoms of premenstrual irritability, reactivity of mood, anxiety, and change in appetite and sleep. Whereas some women experience these symptoms exclusively during the premenstrual phase of the menstrual cycle, others may have premenstrual complaints but actually suffer from mood and anxiety symptoms across the entire menstrual cycle. We sought to determine the extent to which women who seek treatment for premenstrual syndrome (PMS) actually suffer from symptoms of sufficient severity and duration to meet formal criteria for mood or anxiety disorders. Two hundred six women who responded to advertisements for a treatment study of premenstrual dysphoric disorder (PMDD) and who were screened by telephone for study eligibility were included in the current investigation. A telephone questionnaire keyed to the Structured Clinical Interview for Diagnosis (SCID-I/P) was used to screen for the presence of current mood and anxiety disorders. Approximately 39% (n = 80) of respondents met criteria for mood or anxiety disorders or both. Mood disorders were noted almost twice as commonly as anxiety disorders. The high prevalence of mood disorders in the sample underscores the need for clinicians to be aware of the overlap between reported PMS symptoms and underlying depressive disorder. Given that early identification and treatment of mood disorder can increase the likelihood of recovery and lower risk for recurrent illness, clinicians should have a low threshold for ruling out mood and anxiety disorders in women with complaints of premenstrual symptoms.

Anxiety Disorders↗
PubMed1999

Serum concentrations of antidepressants and benzodiazepines in nursing infants: A case series.

OBJECTIVE: The relative risk of psychotropic medication use in women with puerperal psychiatric illness who are breastfeeding has yet to be quantified adequately. Although the emotional and medical benefits of breastfeeding and adverse effects of maternal depression on infant development are well described, how these absolute benefits weigh against the potential effects of psychotropic drug use during lactation to ultimately guide clinical decisions is still unclear. The objective of this report was to evaluate the extent that psychotropic medications were present in the serum of infants breastfed by mothers treated with antidepressants and benzodiazepines. DESIGN: Serum samples were obtained from 35 nursing infants whose mothers were treated with psychotropic medications while breastfeeding. When a detectable concentration of medication was reported, information regarding infant behavior was obtained by maternal report. SETTING: The Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital serves as a regional consultation center for the treatment of psychiatric disorders during pregnancy and the postpartum period. PATIENTS: Subjects were mothers referred to the Perinatal Psychiatry Program for consultation regarding the relative safety of psychotropic medication use while breastfeeding. PRIMARY OUTCOME MEASURES: Presence of detectable levels of medication in infants whose mothers breastfed while taking psychotropic medications during pregnancy and/or during the puerperium and the well-being (based on maternal report) of infants who had detectable serum concentrations of medication. RESULTS: Seventy-four percent (n = 26) of infants had serum medication concentrations below the laboratory limit of detection (assay sensitivity 5-50 ng/mL). In the remaining 26% of the sample (n = 9), serum concentrations of psychotropic medications and/or active metabolites were detected. In each of these cases, infants had been exposed to the medication during pregnancy. Medications were not detected in infant serum when mothers had taken these agents solely during the postpartum period. No readily apparent difficulties with the infants were reported by mothers. CONCLUSIONS: These data support the low incidence of infant toxicity and adverse effects associated with antidepressant and benzodiazepine use during breastfeeding. These data also suggest that infant serum monitoring is helpful in the assessment of medication exposure in children of mothers who breastfeed while using psychotropic medications. Given the limited accumulated data regarding serum concentrations of psychotropic medications in breastfeeding infants, no single agent seems to be safer than another. Therefore, choice of pharmacologic treatment should be guided by the likelihood that it will result in restoration of maternal psychiatric well-being.

Antidepressive Agents↗
PubMed1998

Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge?

A growing body of literature describes the effects of estrogen and other gonadal steroids on the central nervous system. The ability of estrogen to modulate serotonergic function, in particular, raises the possibility that sex steroids may play a role in the mechanisms associated with depression and its treatment. This review will focus on those aspects of the estrogen-serotonin interaction that relate to possible increased vulnerability to affective disorders and on hormonal treatments that may be clinically applicable to women. After a discussion of the potential relationship between estrogen and mood disorders across the female life cycle, a model is proposed in which differential sensitivity to mood disorders explains the differential response by some women to periods of normal hormonal changes. Possible serotonin receptor-mediated and intracellular mechanisms by which estrogen may exert its effects on mood are also reviewed. These are compared to putative mechanisms of standard antidepressant effect. Lastly, treatment studies in which estrogen has been used as 1) monotherapy for depression, 2) an augmentation strategy, or 3) a prophylactic intervention against recurrence of depression are reviewed.

Antidepressive Agents↗
PubMed1998

Micro-sequencing strategies for the human A33 antigen, a novel surface glycoprotein of human gastrointestinal epithelium.

Monoclonal antibody (mAb) A33, which recognizes a M(r) approximately 43,000 differentiation antigen (A33) expressed in normal human colonic and small bowel epithelium as well as in 95% of colon cancers, shows specific targeting of colon cancer in humans and is currently being evaluated for clinical use. Here, we describe strategies for the purification and structural analysis of the A33 antigen from the human colorectal carcinoma cell lines LIM1215 and SW1222. Edman degradation of the intact protein and nine peptides, derived by proteolytic digestion of the A33 antigen with Asp-N endoproteinase, thermolysin, trypsin and pepsin followed by micropreparative reversed-phase high-performance liquid chromatography, allowed the unambiguous sequence assignment of 153 amino acid residues; these data reveal one N-glycosylation sequeon in Asp-N endoproteinase peptide D4, and a disulfide linkage between peptides D1 and D4. This amino acid sequence information has facilitated the cloning and subsequent sequencing of a cDNA for the A33 antigen which demonstrates that it is a novel human cell surface molecule of the immunoglobulin superfamily.

Amino Acid Sequence↗
PubMed1998

Psychotropic drug use during pregnancy: weighing the risks.

Although psychotropic drugs have not been tested or approved by the Food and Drug Administration for use during pregnancy, some women continue to take these medications while they are pregnant, particularly since mood and anxiety disorders cluster in women during childbearing years. The relative risks and benefits of drug therapy for these women must be weighed with each patient and treatment limited to those situations in which risks to mother and fetus from the disorder are presumed to exceed the risk of drug treatment. Risks of psychotropic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer term neurobehavioral sequelae. Of growing concern is the risk of untreated psychiatric disorder as it may potentially affect fetoplacental integrity and fetal central nervous system development. Coordination of care with the patient, her husband or partner, and the obstetrician is essential, as is careful medical record documentation when treating pregnant patients with psychiatric disorders.

Antidepressive Agents↗