Amniotic fluid and umbilical cord blood concentrations of antidepressants in three women.

BACKGROUND: Pregnancy and the postpartum period are a time of increased risk for women to develop mood disorders. As such, the reproductive safety data on antidepressant use during pregnancy have rapidly expanded over the last decade; however, there is relatively sparse information on maternal/fetal exchange of these medications and no data reporting their concentrations in amniotic fluid. METHODS: We report on three women treated during pregnancy with fluvoxamine, sertraline, and venlafaxine, respectively. Amniotic fluid at amniocentesis and umbilical cord blood and maternal blood at delivery were collected and analyzed for antidepressant concentrations using high performance liquid chromatography with UV detection. RESULTS: Antidepressant and metabolite concentrations were detectable in all amniotic fluid samples, though parent compound concentrations were less than maternal serum and umbilical cord blood concentrations. No adverse effects of the medication were reported. CONCLUSIONS: The presence of these antidepressants in amniotic fluid suggests that fetal exposure to these medications is continual and may occur through a variety of paths, thus accounting for increased fetal exposure. These paths include circulatory via placental passage, gastrointestinal via fetal swallowing, and respiratory secondary to fetal lung absorption.

Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk.

BACKGROUND: This study's goal was to characterize nursing infants' exposure to fluoxetine through breast milk and to identify variables for minimizing such exposure. METHODS: Nursing women on stable daily doses of fluoxetine were recruited into the study. Breast milk, maternal and infant serum concentrations of fluoxetine and norfluoxetine were determined with high-performance liquid chromatography. RESULTS: Nineteen nursing women one with a pair of dizygotic twins participated in the study. The women were on stable daily doses of fluoxetine (10-60 mg/day) and all but two took the medication during the last trimester of pregnancy. Fluoxetine was detectable in 30% (n = 6) of the nursing infant sera (< 1-84 ng/mL), whereas norfluoxetine was found in 85% (N = 17) (< 1-265 ng/mL). Peak breast milk concentrations occurred approximately 8 hours after maternal dosing and predicted norfluoxetine concentrations in infant serum. Maternal serum fluoxetine and norfluoxetine concentrations correlated highly with infant norfluoxetine concentrations. A daily maternal fluoxetine dosage of 20 mg or lower was significantly less likely to produce detectable concentrations of either fluoxetine or norfluoxetine in infants compared to higher daily dosages. No adverse effects were reported in any infant. CONCLUSIONS: Our findings demonstrate that maternal serum and peak breast milk concentrations of fluoxetine and norfluoxetine predict nursing infant serum norfluoxetine concentrations. In nursing women taking 20 mg/day or less of fluoxetine, infant serum concentrations were typically low.

Amish Study, I: Affective disorders among the Amish, 1976-1980.

The authors review the goals, methods, sample, and selected epidemiologic findings from a collaborative study of affective disorders among the Amish. This culturally and genetically homogeneous population (N = 12,500) constitutes an excellent research setting for psychiatric epidemiologic and genetic study. Alcoholism, drug abuse, and sociopathy did not complicate the study because they are culturally prohibited. During 1976-1980, 112 active cases of mental illness were identified; 71% received diagnoses of major affective disorder. Equal numbers of men and women received diagnoses of unipolar illness, and slightly more men than women were diagnosed as having bipolar illness.

Amish Study, II: Consensus diagnoses and reliability results.

Reliability of diagnosis is central to genetic research on mental illness. In the Amish Study of affective disorders, consensus diagnoses were derived by a psychiatric board using the Research Diagnostic Criteria (RDC). To verify the reliability of diagnoses, the authors 1) studied how well board members followed RDC procedures, 2) compared diagnoses based on abstracted medical records with those based on full medical records, 3) compared diagnoses based on the two data sources--abstracted medical records and the Schedule for Affective Disorders and Schizophrenia-Lifetime Version--and 4) studied diagnostic stability to determine validity of diagnosis. The results of these substudies demonstrate a high concordance of diagnosis.

Amish Study, III: the impact of cultural factors on diagnosis of bipolar illness.

In the Amish Study of affective disorders, 79% of the 28 active bipolar I patients, diagnosed according to Research DIagnostic Criteria, previously had received hospital record diagnoses of schizophrenia. Both cultural and clinical factors hindered correct diagnosis, and cultural influences particularly complicated the interpretation of the manic symptoms of grandiosity and excessive involvement in activities. Other factors central to misdiagnosis were form of thought (flight of ideas), content of thought (grandiose and religious delusions), paranoid features, and the failure to recognize the presence of a manic syndrome.

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.

Immunologic studies in two patients with persistent lymphocytic thyroiditis, thyrotoxicosis, and low radioactive iodine uptake.

Two patients with persistent lymphocytic thyroiditis and thyrotoxicosis were studied. Both patients presented with severe hyperthyroidism of nine months' duration and had nontender, small thyroid glands. Uptake of radioactive iodine (131I) was consistently low. Serum thyroxine and triiodothyronine levels remained elevated without remission until thyroidectomy. The serum thyroglobulin level was normal, but testing for microsomal antibody gave weakly positive results in one case. Thyroglobulin and thyroid stimulatory antibodies were not found. The ratio of helper to suppressor T cells was elevated in one case. Neither patient showed response to propranolol, prednisone, or iodine. Light microscopic and immunohistologic studies showed severe lymphocytic thyroiditis with formation of secondary lymphoid follicles. Lymphocytes were predominately T cells (OKT11-positive), primarily helper/inducer T cells (OKT4-positive). Hyperplastic nodules contained high immunoreactive thyroglobulin and thyroxine levels. Aberrant thymus was seen within the thyroid. These studies suggest the possibility of intrathyroidal stimulation and hydrolysis of thyroglobulin within thyroid cells and also support the hypothesis that T and B cell immunoregulatory defects are important in the pathogenesis of this disease.

Chronic glomerular microangiopathy complicating metastatic carcinoma.

Six cases of metastatic carcinoma associated with chronic glomerular microangiopathy and renal failure are reported. All had prominent subendothelial lucent zones and double-contoured glomerular basement membranes. There was no immunohistologic or ultrastructural evidence for immune complex entrapment in glomeruli. By immunohistology, material antigenically related to fibrin or fibrinogen was identified in glomerular basement membranes despite a paucity of typical fibrillar fibrin. Four patients received mitomycin C before the onset of renal disease, and one patient received chemotherapy other than mitomycin C before development of renal failure. One patient had no chemotherapy but was given radiotherapy, which did not include the kidneys in the irradiated field. These six cases emphasize the diverse pathophysiologic mechanisms by which glomerular microangiopathy may arise in metastatic carcinoma.

Screening for dyslipidemia. Practice parameter.

Screening for serum lipid disorders is recommended by numerous specialty societies to identify patients at risk for coronary heart disease (CHD). The best screening tests will identify patients at highest risk for CHD who would benefit from intervention. This report discusses an appropriate test panel to use as the initial screen on a healthy outpatient population, and the required accuracy and precision of the tests from the Laboratory Medicine perspective. Controversy exists regarding which methods to use and at what age testing should begin. The following parameters will be modified as studies continue and new tests are developed. The recommendations are as follows: (1) Total serum cholesterol (TC) and high density lipoprotein-cholesterol (HDL-C) are presently the recommended screening tests for dyslipidemia in the general population; (2) The National Cholesterol Education Program (NCEP) recommends measuring TC and HDL-C in adults with a single sample at 5-year intervals beginning at age 20; (3) The NCEP recommends measuring TC in children with at least one parent having TC > or = 6.24 mmol/L (> or = 240 mg/dL); (4) The NCEP recommends a lipoprotein analysis consisting of a 12-hour fasting TC, HDL-C, triglyceride, and estimated low density lipoprotein-cholesterol (LDL-C) in adults with the following results: (a) TC > or = 6.24 mmol/L (> or = 240 mg/dL); (b) borderline TC of 5.20-6.23 mmol/L (200-239 mg/dL) and HDL-C < 0.91 mmol/L (< 35 mg/dL) or two or more risk factors; (c) desirable TC of < 5.20 mmol/L (< 200 mg/dL), but HDL-C < 0.91 mmol/L (< 35 mg/dL); (5) The NCEP recommends a lipoprotein analysis in children with documented CHD in a parent or grandparent, or in children that have a TC of > or = 5.20 mmol/L (> or = 200 mg/dL); (6) Two or three separate lipoprotein analyses should be done to confirm the LDL-C result before therapeutic intervention. Specimens should be tested from 1 to 8 weeks apart and the results averaged to account for physiologic variability; (7) Enzymatic methods are preferred for TC determination, and should be standardized and traceable to the reference method and materials at the Centers for Disease Control and Prevention (CDC); (8) The analytic method for TC should have a bias against the reference method of < 3% and a within laboratory reproducibility of < 3% coefficient of variation; (9) Chemical precipitation methods are preferred for HDL-C determination.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of DNA cytometry methods for benign and malignant thyroid tissue.

DNA measurements of 46 thyroid specimens were performed by use of fresh tissue for flow cytometry and formalin-fixed paraffin-embedded tissue for flow and static cytometry. The tissue included four histopathologic subgroups, i.e., 19 colloid goiters, 7 papillary carcinomas, 10 follicular adenomas, and 10 follicular carcinomas. The methods measured DNA index and the percentage of cells in S-phase for each subgroup. There was a strong correlation between the methods for DNA-index measurements. In three cases, tissue interpreted as diploid by one method was aneuploid by another method. The S-phase measurements were not reproducible between the methods because of the low percentage of cells in S-phase (mean: 2.6%; range: 0.0-7.5% overall). Aneuploid cells were rare in nodular goiter (2 of 19 cases, 10.5%) but were increasingly present in subsequent subgroups, i.e., 2 of 7 papillary carcinomas (28%), 3 of 10 follicular adenomas (30%), and 6 of 10 follicular carcinomas (60%).

Diagnosis and localization of prostate carcinoma by fine-needle aspiration cytology and correlation with histologic whole-organ sections after radical prostatectomy.

Twenty-nine patients with clinical stage T1-2, NO, MO prostate carcinoma were treated by retropubic radical prostatectomy. Diagnosis was made by fine-needle aspiration biopsy from six to eight separate sectors of the prostate. At the time of biopsy, diagrams of the palpated organ were drawn, depicting the location of the lesion and the site of each biopsy. Without the examiners' knowledge of cytologic data, extirpated prostate glands were examined with whole organ histologic sections, and carcinomas were scored according to the method of Gleason. The location and extent of all typical and malignant foci were mapped on a standard diagram. The results of preoperative cytologic examination were compared with postoperative histopathologic findings, showing a tendency toward underestimation of both the extent and degree of differentiation of the carcinomas during cytologic examination. In no case were these parameters overestimated during cytologic examination. The Gleason score correlated well with the presence of capsular and seminal vesicle invasion.

Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories.

OBJECTIVE: A priority for research on manic-depressive or bipolar I disorder (BPI) for children and adolescents has been to search for early predictors of the illness. METHOD: Medical record data were reviewed and systematically coded for a sample of 58 adult patients (32 males/26 females) with confirmed diagnoses of BPI to identify prodromal features and possible patterns of symptoms from the Amish Study. RESULTS: The most frequently reported symptoms included episodic changes in mood (depressed and irritable) and energy plus anger dyscontrol, with no significant gender differences. A progression of ages is seen for the most commonly reported symptoms prior to age 16. The time interval was 9 to 12 years between appearance of the first symptoms and onset of a documented BPI syndrome. CONCLUSIONS: The data suggest testable hypotheses about specific symptoms and behaviors that may be useful for the early detection of children at highest risk for developing manic-depressive disorder.

Differential use of vocal and gestural communication by chimpanzees (Pan troglodytes) in response to the attentional status of a human (Homo sapiens).

This study examined the communicative behavior of 49 captive chimpanzees (Pan troglodytes), particularly their use of vocalizations, manual gestures, and other auditory- or tactile-based behaviors as a means of gaining an inattentive audience's attention. A human (Homo sapiens) experimenter held a banana while oriented either toward or away from the chimpanzee. The chimpanzees' behavior was recorded for 60 s. Chimpanzees emitted vocalizations faster and were more likely to produce vocalizations as their 1st communicative behavior when a human was oriented away from them. Chimpanzees used manual gestures more frequently and faster when the human was oriented toward them. These results replicate the findings of earlier studies on chimpanzee gestural communication and provide new information about the intentional and functional use of their vocalizations.

The use of bouts and frequencies in the evaluation of hand preferences for a coordinated bimanual task in chimpanzees (Pan troglodytes): an empirical study comparing two different indices of laterality.

Hand preferences for a coordinated bimanual task were assessed in 109 chimpanzees (Pan troglodytes). Hand preference was evaluated for 4 test sessions using bouts and frequencies of hand use to compare the sensitivity of each level of analysis in evaluating individual variation in handedness. Overall, significant population-level right-handedness was found using several different measures of hand use. Handedness indices based on bouts and frequencies were highly and significantly correlated. Moreover, hand preferences were consistent across tests despite efforts to situationally bias preference during each test. Taken together, these data do not support the view that bouts are a better level of analysis for evaluating hand preference. The results further suggest that hand preferences for coordinated bimanual actions are not influenced by situational factors and may reflect an inherent specialization of the left hemisphere for motor skill.

Heart-smart service.

Cardiology patients--direct and ED admits--go to Lancaster General Hospital's Cardiology Admissions Unit (CAU) to receive care until a bed is available in an inpatient unit. The CAU yields high patient volume, positive patient and staff feedback, decreased ED length of stay, prompt initiation of treatment protocols, and more effective discharge planning.

Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications.

The use of antidepressants during pregnancy has undergone considerable scrutiny with respect to safety issues, though limited data with respect to dose management and symptom resolution is available. Previous reports on tricyclic antidepressants (TCAs) have demonstrated the need to adjust maternal dose later in pregnancy to maintain therapeutic serum concentrations. However, there is no data on the dosage of selective serotonin uptake inhibitors (SSRIs) required to maintain symptom resolution in women treated for major depression during pregnancy. The purpose of this study, then, was to assess the medication dosage requirements of SSRIs during this time. In this naturalistic study, pregnant women with a primary diagnosis of major depression were followed prospectively through pregnancy at monthly intervals with symptom assessment. Subjects were included in data analysis if they presented prior to 28 weeks gestation, were treated with SSRI monotherapy, received all psychiatric treatment during the pregnancy at the Emory Pregnancy and Postpartum Mood Disorders Program, and achieved euthymia after initial treatment intervention (CGI = 1 and Beck Depression Inventory (BDI) < 9) during pregnancy or failed to respond after eight weeks of treatment. Medication selection was based on personal treatment history or family treatment history (if any), and the published data on SSRIs in pregnancy. All medication dose adjustments were based on depressive symptoms as measured by the BDI and a psychiatric interview (ZNS). Thirty-four pregnant women were included in final analysis. Two thirds of the subjects (n = 22) required an increase in their daily dose of medication to maintain euthymia. The dose increases occurred at 27.1 +/- 7.1 weeks gestation, with mean BDI scores of 16.4 +/- 9.6, compared to a mean treatment response BDI of 6.9 +/- 5.4. Subject's age, education, past personal and familial psychiatric history were not significantly associated with dose adjustment. These novel data on SSRI daily dose in pregnancy parallels the extant literature with tricyclic antidepressants (TCA). Further work to determine the predictors of dose adjustments will provide guidelines for minimizing fetal exposure to both medication and maternal mental illness.

Bipolar affective disorders linked to DNA markers on chromosome 11.

An analysis of the segregation of restriction fragment length polymorphisms in an Old Order Amish pedigree has made it possible to localize a dominant gene conferring a strong predisposition to manic depressive disease to the tip of the short arm of chromosome 11.

Linkage of bipolar affective disorders to markers on chromosome 11p is excluded in a second lateral extension of Amish pedigree 110.

Linkage between markers on chromosome 11p and bipolar affective disorders can be excluded in a second large lateral extension of the original Amish Pedigree 110. These results, together with previous negative linkage findings, suggest that there is not one single gene on 11p conferring susceptibility for bipolar affective disorders among the Old Order Amish.