Dose-response study and threshold estimation of griseofulvin-induced aneuploidy during female mouse meiosis I and II.

The relative sensitivity of the two meiotic divisions of mouse oogenesis to griseofulvin (GF)-induced aneuploidy was investigated. The first meiotic division was studied by administering GF 4 h after human chorionic gonadotrophin (HCG) injection and analyzing metaphase II (MII) oocytes, whereas study of the second meiotic division involved treating the females 10 h after HCG and analyzing one-cell (1-Cl) zygotes. Data from previous studies have shown that these treatment times represented the most sensitive times for aneuploidy induction during meioses I and II. The statistical analyses of the data showed that the dose-response curves for aneuploidy induction did not differ quantitatively or qualitatively between the two meiotic divisions. The percentages of hyperploid MII oocytes and 1-Cl zygotes were significantly higher (P < 0.001) than in the controls for all doses except 125 mg/kg GF. The highest percentages of hyperploid cells were found after administering 1500 mg/kg GF. However, these percentages were not different (P > 0.05) from those observed after 500 or 1000 mg/kg GF, suggesting saturation of the GF aneuploid target(s). These results suggest that the relative sensitivity to GF-induced aneuploidy between the two meiotic divisions of oogenesis are similar. They also suggest the presence of a lower (125 mg/kg) and an upper 500 mg/kg) threshold for GF-induced aneuploidy.

Are adult children of alcoholics unique? A study of object relations and reality testing.

This self-report questionnaire study revealed that adult children of alcoholics (ACAs, n = 49) were significantly different from adult children from normal families (ACNs, (n = 55) on five of nine Bell Object Relations Reality Testing Inventory (BORRTI; Bell, 1988) scales and from adult children from dysfunctional families (ACDs, n = 48) on the Reality Testing summary score. Both ACAs and ACDs were similar to each other and different from ACNs on Insecure Attachment and on two family background ratings- perceived quality of paternal and maternal caregiving. Discussion of these results plus separate exploratory regression analyses followed.

"Informed consent" interactive videodisc for patients having a colonoscopy, a polypectomy, and an endoscopy.

These "informed consent" interactive videodisc programs use both graphic and live action sequences to describe in detail the diagnostic procedures of Endoscopy, Colonoscopy, and Polypectomy. Both benefits and possible risks are listed and described. After each sequence, the patient is asked whether the explanation is understood and/or whether the patient would like to discuss the procedure in more detail with a physician. The programs were designed for use with marginally literate patients and require no reading ability. Both programs are also ideal for general patient education.

Tubal ectopic pregnancy: a histologic, morphometric, and statistical study.

Pathologists are occasionally asked for medicolegal reasons to estimate the gestational age of an ectopic pregnancy based on morphologic findings. We evaluated the correlation between the gestational age and the maximal diameter of the resected fallopian tube, the average diameter of chorionic villi, the number of chorionic villi per square millimeter of the microscopic section, the number of degenerated villi per square millimeter, the number of syncytial knots per square millimeter, and the average number of layers of cytotrophoblastic cells covering the villi. There was a significant correlation between the diameter of the fallopian tube and the gestational age, with a correlation coefficient of 0.41 and a P value of .05. There was no significant correlation of the gestational age with any of the microscopic parameters measured. The findings indicate that an approximate estimation of the gestational age of tubal ectopic pregnancies may be made using the diameter of the resected fallopian tube.

Reading deficiencies in older patients.

To participate effectively in their health care, older patients often are expected to read a wide variety of materials, including written instructions, brochures, and consent forms. This study quantitates the reading ability of older patients and compares it to that of younger patients. Two hundred seventy-two patients 30 and older were selected from five outpatient clinics at a public teaching hospital and tested for objective reading ability using the Peabody Individual Achievement Test--Revised. The 76 patients 60 and older read significantly worse (grade level 2.9) than the 196 patients younger than 60 (grade level 5.8) (P < 0.0001). Older patients also completed significantly fewer years of school than younger patients (7.3 years versus 10.6 years). Analysis of variance for age categories 30-44, 45-59, 60-74, and 75 and older confirmed declining reading ability and educational status with advancing age. Multiple regression analysis helped show that an equation could be derived to predict reading ability from age, educational status, race, and sex, but the coefficient of determination was so low (r2 = 0.39) that it cannot be considered clinically useful for individual patients. In this study, older patients read significantly worse than younger patients, and a formula that combines age, race, sex, and educational status cannot reliably predict reading ability for individual patients. Most older patients read on a level so low that they cannot be expected to read most commonly used written materials. Routine testing of reading ability may allow more appropriate design and use of written materials.

Assessment of hypoxemia in patients with sleep disorders using saturation impairment time.

A method of recording cumulative nocturnal oxygen desaturation was utilized to develop a quantitative index of nocturnal hypoxemia (SIT index) to provide reference values and distributional properties for apneic and nonapneic sleep-disordered patients. The SIT indices were compared in patients with varying degrees of obstructive sleep apnea (OSA) as determined by traditional methods of counting apneas and hypopneas. We studied 298 patients who were divided into five groups based on the presence and frequency of apnea or sleep-related respiratory deterioration. SIT indices for patient groups and individual patients were compared with the respiratory disturbance index (apneas + hypopneas x 60/total sleep time = RDI) using scatter plots, Kruskal-Wallis analysis of variance, and Mann-Whitney U tests. The OSA and non-respiratory-impaired patient groups had mean SIT values that were significantly different (p < 0.05). Subjects with severe apnea differed (p < 0.05) from subjects with mild and moderate apnea at SIT index thresholds < baseline, < 90, < 80, and < 70% SaO2, but subjects with mild and moderate apnea did not differ statistically from each other at any threshold. In individual patients with similar RDI values, considerable variation in SIT index can be seen, and the reverse is also true. This suggests that using both RDI and SIT may provide complementary information in assessing the severity of OSA.

Timing and dosage of postoperative radiotherapy for squamous cell carcinoma of the upper aerodigestive tract.

Seventy patients who received postoperative irradiation (PI) after curative surgery for stage III or IV squamous cell carcinoma of the upper aerodigestive tract were studied retrospectively to compare the rate of local and regional recurrence (LRR) and the effect of total dose on LRR rate in patients irradiated timely (n = 40) with those who were not (n = 30). Overall, the LRR rate was higher when PI was delayed than when timely (37% vs 20%). No advantage resulted from increasing total dose when PI was delayed; the LRR rate in the primary site and upper neck was 18% with less than 60 Gy and was 26% with 60 Gy or more; the LRR rate in the lower neck was 13% with 50 Gy or less and was 14% with more than 50 Gy. These data seem to corroborate the findings of other investigators regarding the importance of initiating timely PI, but not the observation that a pronounced delay is not detrimental provided higher tumoricidal doses are used.

Characteristics of indigent women with ruptured and unruptured tubal pregnancies.

The diagnosis of tubal pregnancy, whether ruptured or unruptured, often requires a surgical procedure, such as laparoscopy or laparotomy, for confirmation. We compared women with ruptured and unruptured tubal pregnancies to determine whether the clinical presentations, morbidity and surgical complications in the two groups were significantly different. We compared the demographic characteristics, clinical presentations, laboratory findings, morbidity and complications from surgical management in the two groups. Women with ruptured tubal pregnancies had a higher incidence of abdominal pain lasting less than 24 hours, adnexal tenderness and positive culdocentesis from hemoperitoneum as compared to women with unruptured tubal gestations. Abnormal uterine bleeding was observed less frequently in women with ruptured tubal pregnancies as compared to women with unruptured ones despite similar gestational ages at presentation. All the patients with a tubal pregnancy were managed surgically. The morbidity and surgical complication rates in the two groups were not significantly different.

Clomiphene-dexamethasone treatment of clomiphene-resistant women with and without the polycystic ovary syndrome.

We used clomiphene and dexamethasone in 40 infertile women to treat chronic anovulation resistant to the use of clomiphene alone. Eighteen (45%) of the women had the polycystic ovary (PCO) syndrome; the remaining 22 (55%) had clomiphene-resistant anovulation from idiopathic causes. Both groups of women were similar in regard to age, parity, duration of infertility and absence of other causes of infertility besides chronic anovulation. Ovulation could be induced in approximately 90% of the women in each group. Altogether, 19 of 36 women (52.8%) conceived without any side effects or complications. The cumulative probability of conception at nine months of treatment was 87.5% in PCO patients and 46% in the non-PCO group. Clomiphene plus dexamethasone was highly effective in the treatment of clomiphene-resistant anovulation associated with infertility in women with and without the PCO syndrome.

Patient reading ability: an overlooked problem in health care.

Health care workers often assume that patients who have completed a certain grade in school can read at that level. This study examines the relationships between patient reading ability, the last grade completed, and the reading ability necessary to comprehend commonly used written materials. We tested 528 patients during regular visits to seven outpatient clinics serving a predominantly indigent population. In addition, we analyzed the readability of 280 brochures and consent forms used in these clinics. Most patients had reading abilities on a level far below their last grade completed, while almost all materials tested were written on a level far above average patient reading ability. We conclude that patient reading ability should be routinely tested and that written materials should be developed on a level commensurate with patient reading ability.

Rapid assessment of literacy levels of adult primary care patients.

Health education materials, medical instructions, consent forms, and self-report questionnaires are often given to patients with little regard for their ability to read them. Reading ability is rarely tested in medical settings. The Rapid Estimate of Adult Literacy in Medicine (REALM) was developed as a quick screening tool to assist physicians in identifying patients with limited reading skills and in estimating patient reading levels. This information can be used to tailor materials and instructions to patients' abilities. The REALM and the reading sections of the Peabody Individual Achievement Test-Revised and the Slosson Oral Reading Test were used to test reading ability in 207 adults in six public and private primary care clinics. REALM scores correlated highly with those of the standardized reading tests. The REALM, which takes three to five minutes to administer and score, appears to be a practical instrument to estimate patient literacy in primary care, patient education, and medical research.

Use of psychoactive substances by medical students: a survey.

The use and abuse of alcohol and other psychoactive substances is of concern to the medical profession and to medical educators. Sixty-eight members of the sophomore class at LSU Medical Center in Shreveport participated in a substance use survey. Ten students (14.7%) described themselves as abstainers from alcohol consumption. Although none described themselves as heavy or abusive drinkers, 9 (13.2%) drank 6-10 alcoholic beverages on a weekend if there was no examination scheduled for Monday or Tuesday, and 3 (4.4%) consumed more than 10 alcoholic beverages on such a weekend. At a large school social event, 9 students (13.2%) drank 6-10 alcoholic beverages and 3 (4.4%) drank more than 10 alcoholic beverages during the event. Nine students (13.2%) used marijuana at least 1-3 times per year. Tobacco was used by 17.6% of the students sampled. Only 4 students (5.9%) avoided caffeine completely. Twelve students (17.6%) drank 5-10 caffeinated beverages daily. The use of cocaine (2.9%), amphetamines (4.5%), and unprescribed sedatives (6%) was small in this student sample. More education concerning effects of psychoactive substances is encouraged.

Antinuclear antibodies in sickle cell disease.

The frequency of antinuclear antibodies (ANA) and other antinuclear factors was prospectively evaluated in patients with sickle cell disease (SCD). Ten of 44 patients studied (22.7%) had positive ANA determinations at titers greater than or equal to 1:40 compared to 3 of 46 healthy controls (6.5%; p less than 0.03). Eight SCD patients had ANA titers of 1:160 or greater compared to none of the controls (p less than 0.003). No antibodies directed against other nuclear factors were found. An analysis of the patient histories revealed no statistical differences between the ANA-positive and ANA-negative SCD patients when correlated with disease activity.

Antinuclear antibodies and anticytoplasmic antibodies in bronchial asthma.

The presence of antinuclear antibodies and anticytoplasmic antibodies was evaluated in the sera of 50 patients with bronchial asthma and 35 matched control subjects with miscellaneous medical diseases with the use of an indirect immunofluorescent assay with HEp-2 cells as substrate. The results were compared to age, sex, atopic status, dose, and duration of the antiasthmatic medication, immunotherapy, severity of the disease, and presence or absence of myalgia. The patients had mild to moderate asthma. The incidence of fluorescent anticytoplasmic antibodies (FACA) in the sera of patients with asthma was statistically significant (p = 0.02) in comparison to FACA in the sera of the control subjects. The combined incidence of fluorescent antinuclear antibodies (FANA) and FACA was found to be significantly higher among atopic subjects with asthma (p = 0.03) and the subjects with asthma and with myalgia (p less than 0.05). The 20% incidence of FACA in this group of subjects with asthma was significantly greater (p less than 0.0001) than the reported 2.7% incidence of FACA in a group of patients with various rheumatologic diseases. Variables, such as dose and duration of antiasthma medications and immunotherapy did not appear to influence the presence of FANA and FACA in their sera. The significance of positive FANA and FACA in this group of subjects with asthma is not known and needs to be evaluated by long-term studies.

Effects of chronic ethanol and diet treatment on urinary folate excretion and development of folate deficiency in the rat.

Because the folate deficiency of chronic alcoholism has been proposed to result from ethanol-induced effects on metabolism or urinary excretion of folate, the present study was designed to evaluate the role of chronic ethanol-induced urinary folate loss on folate homeostasis in the rat. Male Sprague-Dawley rats were fed nutritionally sufficient liquid diets for 12 wk with or without ethanol, folate and sulfonamide. Urinary folate excretion was increased in ethanol-fed rats consuming folate-containing diets, but not in rats fed folate deficient diets. Consumption of folate-deficient diets led to a rapid decrease in urinary folate excretion, suggesting renal adaptation to conserve folate. Tissue and plasma levels of folate were mostly unaffected by ethanol ingestion in rats fed folate-containing diets. Ethanol treatment did not consistently enhance tissue folate depletion in rats fed folate-deficient diets. The results suggest that in rats consuming diets containing high levels of folate, chronic ethanol ingestion increased urinary folate excretion, but not to a sufficient magnitude to consistently affect folate homeostasis.

Duration of the suppressive effect of tricyclic antidepressants on histamine-induced wheal-and-flare reactions in human skin.

The antihistaminic properties of the tricyclic antidepressants have been recognized since these compounds were first developed. Antidepressants, which are equally effective for treating depression or used in the treatment of chronic urticaria, have varying in vitro antihistaminic properties. We compared the duration of H1-receptor blockade by two tricyclic antidepressants, doxepin (the most potent antihistamine) and desipramine (the least potent antihistamine), in a single dose, double-blind, noncrossover study. After baseline prick test with histamine phosphate 1:1000 by Multitest (Lincoln Diagnostics, Decatur, Ill.), the suppression of cutaneous histamine-induced wheal-and-flare responses were measured daily for 7 days in 33 healthy volunteers who were randomly administered a single 25 mg dose of oral desipramine or doxepin. Significant differences in the suppression of the wheal-and-flare responses to histamine between the two drugs were noted (p less than 0.05) during the first 3 days. Desipramine suppressed the wheal for 2 days and flare for 1 day. Doxepin suppressed the wheal for 4 days and flare for 6 days. Our results suggest doxepin should be withheld for at least 7 days before allergy skin testing.

Assessment of response to oral metaproterenol sulfate by forced oscillation in young children.

The dose response characteristics and side effects of three doses of oral metaproterenol sulfate (MS) (0.4, 0.6, and 0.8 mg/kg) were compared with a placebo in ten asthmatic children (3 to 6 years). The bronchodilator efficacy was objectively assessed by evaluating the decrease in mean total respiratory resistance (MTRR) using Oscillaire. The mean percentage changes from baseline in MTRR showed that MS in all three doses was more effective than placebo. Lack of objective demonstration of bronchodilator efficacy, concern for possible side effects and uncertainty of the precise dosage for adequate bronchodilation are some of the factors that account for the lack of specific dosage recommendations for bronchodilators such as oral metaproterenol sulfate in children under 6 years of age. Until recently, it was not possible to objectively measure the response to bronchodilators in children below 6 years of age because of their inability to reliably perform forced expiratory maneuvers required for spirometry and their unwillingness to have airway resistance (or conductance) measurements by body plethysmography. Direct measurements of airflow resistance have been made in children with a pneumotachograph at the mouth and a balloon in the esophagus to record transpleural pressure changes; however, these techniques are invasive and require sedation. Total respiratory resistance and reactance of the respiratory system, as measured by forced oscillation technique, are pulmonary function tests that can be performed in young children who are unable to cooperate with conventional spirometric maneuvers.

Childhood depression: an overlooked problem in family practice.

To investigate the incidence and correlates of childhood depression in a family practice clinic, Kovacs Childhood Depression Inventory (CDI) was administered to 64 patients, aged 6 to 12 years. Accompanying parents completed the short form of Beck's Depression Inventory (BDI) and reported on the children's behavior problems. One half of the children studied scored within the depressed range on the CDI. Thirty-nine percent of the parents scored at least mildly depressed on the BDI. Depression appeared to cluster in families. Every parent who scored in the severe depression range was accompanying a child who rated himself or herself as depressed. All parents who scored above the cutoff for mild depression rated their children as having behavior problems. Children's self-reported depression was also related to negative parental rating of the children's behavior.