Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.

alpha-Globin is encoded by the two adjacent genes, alpha 1 and alpha 2. Although it is clearly established that both alpha-globin genes are expressed, their relative contributions to alpha-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in alpha-globin gene activity secondarily to the loss of function of one or more of these genes (alpha-thalassemia [Thal]) have not been directly investigated. This study further defines the expression of the two human alpha-globin genes by determining the relative levels of alpha 1 and alpha 2 mRNA in the reticulocytes of normal individuals and in individuals heterozygous for the common 3.7-kilobase deletion within the alpha-globin gene cluster that removes the alpha 2-globin gene (the rightward type alpha-Thal-2 deletion). To quantitate accurately the ratio of the two alpha-globin mRNAs, we have modified a previously reported S1 nuclease assay to include the use of 32P end-labeled probes isolated from alpha 1- and alpha 2-globin complementary DNA recombinant plasmids. In individuals with a normal alpha-globin genotype (as determined by Southern blot analysis [alpha alpha/alpha alpha]), alpha 2-globin mRNA is present at an average 2.8-fold excess to alpha 1. In individuals heterozygous for the rightward type alpha-Thal-2 deletion (-alpha/alpha alpha) the alpha 2/alpha 1 mRNA ratio is 1:1. These results suggest that the loss of the alpha 2-globin gene in the alpha-Thal-2 deletion is associated with a 1.8-fold compensatory increase alpha 1-globin gene expression.

Characteristic morphologic abnormality of harlequin ichthyosis detected in amniotic fluid cells.

We have examined cells from amniotic fluid obtained at 17 and 21 weeks' gestation and fetal skin biopsy samples from a fetus at risk of harlequin ichthyosis by light and electron microscopy. Clumps of abnormally keratinized cells that had a large number of lipid droplets in the cytoplasm were seen within both the 17- and 21-week amniotic fluid cell pellets. The cells in these clumps were similar to the thick layers of keratinized cells observed in the skin biopsy and autopsy samples. Morphologic examination of the fetal skin biopsy samples obtained at 21 weeks gestation revealed the characteristic changes of harlequin ichthyosis. The intraepidermal portions of hair canals had an excessive number of layers of keratinized cells. Normal lamellar granules were absent but abundant membrane-bound vesicles of a similar size and a number of dense bodies were observed in the cells of the upper intermediate layers of the epidermis. Autopsy skin samples of the terminated fetus at the twenty-third week of gestation showed structural changes that corresponded to those of the amniotic fluid cells and the fetal skin biopsy samples, although the periderm was gone in all the regions. Our findings of amniotic fluid indicate that the characteristic epidermal abnormality of harlequin ichthyosis has been expressed at 17 weeks gestation in some parts of the body or structures of fetal skin (e.g., hair canals) that keratinize before interfollicular epidermis. Moreover, the results suggest that harlequin ichthyosis can be detected in utero by morphologic analysis of amniotic fluid cells obtained by amniocentesis.

Neural tube defects: issues in prenatal diagnosis and counselling.

Neural tube defects are a heterogeneous group of malformations resulting from failure of neural tube closure during early embryogenesis. They range widely in severity from the lethal condition of anencephaly, to severely disabling meningomyeloceles, to completely surgically correctable meningoceles. Occurring in 1.4 to 1.6 per 1000 live births, neural tube defects rank second only to cardiac abnormalities as a cause of major congenital malformations in the United States. Technical developments over the past decade have enabled better detection of these conditions prenatally. Understanding of the etiology, neonatal treatment, and potential prevention of neural tube defects is increasing. Further, the ethical issues of treatment and screening are being widely discussed in both news magazines and the Congressional Record. Thus, it is timely to review this important area of prenatal counselling, diagnosis, and management.

Maternal acetaminophen overdose at 15 weeks of gestation.

Acetaminophen is a common drug used in pregnancy. A 32-year-old woman ingested 64 g of acetaminophen at 15 weeks of gestation. Treatment with N-acetylcysteine was given within 24 hours. The patient nonetheless developed severe hepatic necrosis and her hospital course was complicated by adult respiratory distress syndrome. With aggressive supportive treatment, the mother survived and delivered a viable infant at 32 weeks' gestation. The possible mechanisms of acetaminophen toxicity in the mother and the fetus are discussed.

Prospective evaluation of a risk scoring system for predicting preterm delivery in black inner city women.

Nine percent of United States births are preterm. The ability to efficiently identify women destined to deliver before term would enable obstetricians to initiate early intervention. The Papiernik-Creasy risk scoring system is being extensively applied for this purpose, without prospective validation in this country. We evaluated prospectively its ability to predict high risk women in a black inner city population, when applied once early in pregnancy. The system, based on social, past medical, and current pregnancy problems, failed to identify at-risk patients. Adjusting the score cutoff and reweighting factors with discriminate analysis did not improve the predictive value. Analysis of an additional 60 social, demographic, and medical factors failed to produce a useful alternative risk assessment tool. We suggest that risk scoring systems such as these may not be helpful in socioeconomically at-risk populations.

Intermittent weekly contraction monitoring to predict preterm labor in low-risk women: a blinded study.

To assess the predictive value of uterine activity as a marker for subsequent preterm labor, 139 black, inner city women were monitored at least three times for 1 hour between 28-32 weeks' gestation using a portable tocodynamometer. All had singleton gestations and gave no previous history of preterm labor or delivery. They were monitored between 8 and 10 AM while sitting in the clinic waiting area. Uterine activity records, numbered randomly, were transmitted by telephone to a site remote from the hospital. No one having any clinical contact with the participants saw or received feedback regarding the contraction data. Tocodynamometry records were then mailed to another center where they were read by one investigator blinded to all clinical information. The mean contraction frequency during the single hour of weekly testing was significantly greater for the 16 women who developed preterm labor than for women who delivered at term at each point between weeks 28-32. Using greater than six contractions per hour on at least one occasion between 28-32 weeks' gestation as a predictor would have identified 12 of 16 women (sensitivity 75%) who subsequently developed preterm labor. This contraction frequency was noted in 26 of 123 women (21%) who labored at term (specificity 79%; P = .0003).

Controlled trial of a Preterm Labor Detection program: efficacy and costs.

Patient education regarding the signs and symptoms of preterm labor combined with frequent clinical evaluations has been advocated as a means to reduce preterm births. Over a 3.5-year period, the risk for preterm labor was determined in 943 indigent black inner-city women using the Papiernik-Creasy scoring system. High-risk women were allocated randomly to a Preterm Labor Detection Clinic or to serve as high-risk controls. Women with lower risk scores served as low-risk controls. Women from both control groups were not informed of their risk status, and both groups received prenatal care in standard obstetric clinics. Women accepting the Preterm Labor Detection Clinic Program received comprehensive patient education and were seen weekly starting at 22 weeks' gestation. Despite this extensive outpatient program, there were no significant differences between the high-risk groups with respect to mean gestational age at delivery, mean birth weight, or percentage delivering before term as a result of preterm labor or premature rupture of membranes (PROM). Evaluations of inpatient charges revealed no significant differences due to participation in this program, although outpatient clinic utilization and charges were increased significantly for Preterm Labor Detection Clinic patients. Failure of this program to reduce preterm birth may relate to the relatively low overall rate of women presenting in preterm labor with advanced cervical dilation. In contrast, high rates of PROM and fetal death occurred in all three study groups.

Antenatal care of the patient with previous preterm premature rupture of membranes.

Although there is a 21% recurrence risk for PPROM, little research has been directed to the obstetric management of women with prior PPROM. This article reviews indirect information regarding risk assessment, diet, lifestyle factors, and infections. A management plan is suggested.

Suction sampling technique for obtaining standardized cytologic specimens from the oral mucosa.

To enhance the value of exfoliative cytology for the study of the oral mucosa, a simple apparatus was developed to permit adequate sampling of a specific site so that samples collected on different occasions could be compared. The device essentially consists of a collecting cup connected to a blood collection evacuation system. The collecting cup is a modified female half of a stainless-steel filter holder supporting a 13-mm-diameter cellulose filter of 0.05-microns pore size. Suction pressure is applied by means of a 10-mL glass tube of premeasured vacuum. After positioning the collecting cup on the selected site on the buccal mucosa, the vacuum (440 mm Hg) is applied for five seconds. The mucosa is drawn in against the filter, producing a monolayered imprint of cells. This sample may be disengaged from the filter by agitation into a solution; this allows quantitative cytologic studies, such as the measurement of cell numbers by an electronic counter or the estimation of the areas of cells and nuclei by computer-aided image analysis of Cytospin preparations. Five separate samplings from each of three test subjects produced a harvest of 3,000 to 7,000 epithelial cells per sample; the cellular areas ranged from 784 to 1,052 sq microns while the nuclear areas ranged from 18.4 to 21.8 sq microns.

Acute herpetic stomatitis: referrals to Leeds Dental Hospital 1978-1987.

The clinical data of 102 patients referred to Leeds Dental Hospital from 1978 to 1987 with acute herpetic stomatitis confirmed by laboratory investigations were analysed. No gender difference was found. Differences in age distribution were marked. Only 5% of patients were aged less than 11 years, whereas the majority of cases (51%) occurred during the third decade. Statistical analysis confirmed a general trend for the mean age of patients to have increased progressively over the 10-year period.

Differences in in vitro growth of epithelium from inflammatory and developmental odontogenic cysts.

Ninety-three odontogenic cysts, 42 of inflammatory and 51 of developmental origin, were grown in vitro from explants and/or cell suspensions. There was little difference in the success rate of culturing epithelium from explants of dentigerous cysts (N = 28) or odontogenic keratocysts (N = 23) (approximately 75% and 87%, respectively) and the dentigerous cyst grew particularly well from suspensions (N = 11) (91%) compared with the keratocyst (N = 19) (58%). Epithelium from developmental odontogenic cysts grew much better in vitro than did cysts of inflammatory origin (56 to 58% from explants and 19 to 25% from suspension). From this work there is little evidence to support previous statements that the dentigerous cyst cannot be grown from explants, or that the odontogenic keratocyst has 'aggressive' growth characteristics.

The cause and management of burning mouth condition.

This paper reviews the clinical presentation and many causes of burning mouth condition. A diagnostic approach and some management procedures that include eliminating all oral irritants, correcting predisposing systemic disease, and most important of all, allaying anxiety that induces parafunctional mouth habits. The term "burning mouth condition" (BMC) is considered more appropriate than the word "syndrome" for this common and troublesome complaint.